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Harold Ramis not only may be the most successful comedy writer-director that Chicago has produced, but some wouldn’t even confine that statement to Chicago.

“Harold was clearly the most successful comedy writer-director of all time,” said Tim Kazurinsky, who followed Ramis at Second City and later became his friend. “The number of films that he has made that were successful, that were blockbusters, nobody comes close. Even in light in of that, he was more successful as a human being.”

Ramis’ career was still thriving in 1996, with “Groundhog Day” acquiring almost instant classic status upon its 1993 release and 1984’s “Ghostbusters” ranking among the highest-grossing comedies of all time, when he decided to move his family back to the Chicago area, where he grew up and had launched his career.

On Monday, Ramis was surrounded by family in his North Shore home when he died at 12:53 a.m. of complications from autoimmune inflammatory vasculitis, a rare disease that involves swelling of the blood vessels, said his wife, Erica Mann Ramis. He was 69.

Ramis’ serious health struggles began in May 2010 with an infection that led to complications related to the autoimmune disease, his wife said. Ramis had to relearn to walk and suffered a relapse of the vasculitis in late 2011, said Laurel Ward, vice president of development at Ramis’ Ocean Pictures production company. He never fully recovered.

Ramis leaves behind a formidable list of achievements, with writing credits on such enduring comedies as “National Lampoon’s Animal House” (which upon its 1978 release catapulted the film career of John Belushi, with whom Ramis acted at Second City), “Stripes” (1981) and “Ghostbusters” (in which Ramis also co-starred), plus such directing efforts as “Caddyshack” (1980), “National Lampoon’s Vacation” (1983), “Groundhog Day” and “Analyze This” (1999).

Previously he was the first head writer (and a performer) on Second City’s groundbreaking television series “SCTV,” and more recently he directed episodes of NBC’s “The Office.”

Ramis’ comedies were often wild, silly and tilting toward anarchy, but they also were cerebral and iconoclastic, with the filmmaker heeding the Second City edict to work at the top of one’s intelligence. This combination of smart and gut-bustingly funny led a generation of comedic actors and filmmakers — including Judd Apatow (“The 40 Year Old Virgin,” “Knocked Up”), Jay Roach (“Meet the Parents,” the “Austin Powers” movies), Peter Farrelly (“There’s Something About Mary,” “Dumb and Dumber”), Jake Kasdan (“Walk Hard: The Dewey Cox Story,” “Orange County,” both of which featured Ramis in small roles) and Adam Sandler (who starred in his own wacky golf comedy, “Happy Gilmore”) — to cite him as a key inspiration.

“When I was 15, I interviewed Harold for my high school radio station, and he was the person that I wanted to be when I was growing up,” said Apatow, who would cast Ramis as Seth Rogen’s father in “Knocked Up” and would produce Ramis’ final movie, “Year One” (2009). “His work is the reason why so many of us got into comedy. We grew up on ‘Second City TV’ and ‘Ghostbusters,’ ‘Vacation,’ ‘Animal House,’ ‘Stripes,’ ‘Meatballs’ (which Ramis co-wrote). He literally made every single one of our favorite movies.”

Ramis also left behind a reputation as a mensch and mentor.

“He’s the least changed by success of anyone I know in terms of sense of humor, of humility, sense of self,” the late Second City founder Bernie Sahlins, who began working with Ramis in 1969, said of him in 1999. “He’s had enormous success relatively, but none of it has gone to his head.”

Ward recalled that when she first began working for Ramis 15 years ago as his assistant, he had to be in California for a month, and he told her that although he didn’t need an assistant out there, she should go anyway because it would be a good experience for her, and he’d make sure her expenses were covered.

“He just did it for me,” she said. “He loved teaching people. He loved helping people. He loved seeing people succeed.”

The son of Ruth and Nathan Ramis, who owned Ace Food & Liquor Mart on the West Side before moving the store and family to Rogers Park, Ramis graduated from Senn High School and Washington University in St. Louis.

For his first professional writing gig, he contributed freelance arts stories to the Chicago Daily News in the mid-1960s.

Richard Christiansen, his Daily News editor (and later Tribune theater critic and entertainment editor), recalled one assignment in which Ramis covered a rock concert attended mostly by authority-scorning teenagers. “When it was over, he noted that the kids came out of the concert, and the parents were waiting for them in their cars to drive them home,” Christiansen said with a laugh. “It was a gift for noticing life’s ironies and twists that distinguished his writing eye at the very earliest.”

Ramis also wrote and edited Playboy magazine’s “Party Jokes” before and during his Second City days. After some time away from Second City, he returned in 1972 and came to a major realization while acting alongside a relative newcomer in the cast.

“The moment I knew I wouldn’t be any huge comedy star was when I got on stage with John Belushi for the first time,” he said in a 1999 Tribune interview. “When I saw how far he was willing to go to get a laugh or to make a point on stage, the language he would use, how physical he was, throwing himself literally off the stage, taking big falls, strangling other actors, I thought: I’m never going to be this big. How could I ever get enough attention on a stage with guys like this?

“I stopped being the zany. I let John be the zany. I learned that my thing was lobbing in great lines here and there, which would score big and keep me there on the stage.”

With his round glasses lending a professorial air, Ramis would become the calm center of storms brewed by fellow actors, playing the bushy-haired, low-key wisecracker to Bill Murray’s troublemaker in “Stripes” and being the most scientific-minded “Ghostbuster.” Later roles included the sympathetic doctor of James L. Brooks’ “As Good as It Gets” (1997) and the charming “Knocked Up” dad, whose dialogue, Apatow said, was almost all improvised.

Ramis followed Belushi from Second City to New York City to work with him and fellow Second City cast member Murray (who would collaborate with Ramis on six movies) on “The National Lampoon Radio Hour.” Those three, Gilda Radner and others also performed in a National Lampoon stage show produced by Ivan Reitman, who produced “Animal House” and directed several Ramis scripts.

Second City co-owner/CEO Andrew Alexander, based in Toronto when he created “SCTV,” said head writer Ramis was largely responsible for what that series became.

“He had a special gift of bringing people along and getting the best out of people and getting people to work together,” Alexander said, adding that when Ramis couldn’t move from Los Angeles to Toronto to write the show’s second season, Alexander moved the entire writing team — John Candy, Joe Flaherty, Eugene Levy, Andrea Martin, Catherine O’Hara, Brian Doyle-Murray and Dave Thomas — to California rather than lose his head writer.

Sahlins, who died in June, said he knew from the start that Ramis “would be an important factor in American comedy. He has all the skills and abilities to be funny and to write funny, but he also is a leader, a very nice guy. He was always looked up to, in Second City to being head writer at ‘SCTV.’ He was never separate from anybody. He was always one of the boys, but he was the best boy.”

Apatow said he was captivated not just by the spirit of Ramis’ movies but also his frequent collaborations with a collective of funny people.

“We noticed this group of friends who were making comedy together — all the ‘SCTV’ people and ‘Saturday Night Live’ people and National Lampoon people — and that seemed the most wonderful community you could ever be a part of,” said Apatow, who has developed his own group of regular collaborators. “In addition to wanting to be comics, we also wanted to make comedies with our friends.”

As zany as Ramis’ early comedies were, they rigorously pursued a theme close to the heart of someone who grew out of the 1960s counterculture: characters rebelling against institutions, be they authoritarian college administrators and pampered rich kids (“Animal House”), a stuffy golf club (“Caddyshack”) or the military (“Stripes”). After the collapse of his first marriage and the flop of his 1986 comedy “Club Paradise” (with greedy developers as the institutional villain), the Jewish-raised Ramis immersed himself in Zen Buddhism.

“It’s my shield and my armor in the work I do,” he said. “It’s to keep a cheerful, Zenlike detachment from everything.”

Ramis’ later directorial efforts — starting with “Groundhog Day” and including “Stuart Saves His Family” (1995), “Multiplicity” (1996), “Analyze This” and his “Bedazzled” remake (2000) — reflect a spiritual striving, exploring individuals’ struggles with themselves more than outside forces.

Comparing his later to earlier comedies, Ramis told the Tribune: “The content’s different, but it comes from the same place in me, which is to try to point people at some reality or truth.”

Ramis used to carry around a sheet titled “The 5-Minute Buddhist,” which sums up such tenets as “The self, the soul, the ego are mental projections, false beliefs ….” Apatow said he got a copy from Ramis and keeps it in his desk.

“He was the nicest man I’ve ever met, and he taught me so much about comedy and about spirituality and about being a good person,” Apatow said.

Ramis had been living in Los Angeles since the late ’70s before he returned to Chicago, basing his production company in downtown Highland Park. He said in 1999 that he was happy to leave the “artificial pressure” of LA.

“I’ve compared it to high school: Am I popular? Am I cool? Am I in? Who’s the in crowd? How do I get into that party?” Ramis said. “These are not things I ever wanted to worry about. Here I’m so liberated from that.”

After unsuccessfully lobbying Billy Crystal and Robert De Niro to film “Analyze This” in Chicago, Ramis finally got his wish to shoot a movie locally with the 2005 dark crime comedy “The Ice Harvest,” which starred Evanston native John Cusack and Billy Bob Thornton.

Until his illness Ramis was out around town a fair amount, whether cheering on the Cubs and leading the occasional “Take Me Out to the Ball Game” or attending theater or appearing at fundraisers or collecting honors. When Second City celebrated its 50th anniversary in December 2009, Ramis joined “SCTV” cast members O’Hara, Levy, Martin, Flaherty, Thomas and Martin Short in a Mainstage set that proved to be the weekend’s hottest ticket.

“That voice, that laugh — he was so much fun to perform with,” Short said. “We were so fortunate because it was the following May that he got sick.”

Ramis was quiet about his illness, but friends did visit, including brothers/Second City cast mates Bill Murray, from whom he’d been estranged for years, and Brian Doyle-Murray, who appeared in seven Ramis movies. Short kept in touch as well, saying he was pleased that his friend was able to attend his Just for Laughs performance in 2011. “He got up out of his wheelchair and showed me his progress,” Short said. “He was frailer in his voice but not in his spirit.”

But the past year, Short and other friends and family said, was tough, and now they are dealing with the loss of such an outsized personality.

“He was like the campfire that we all gathered around for light and warmth and knowledge,” said his daughter, Violet Stiel.

“That’s the truth,” his wife added.

In addition to his wife and daughter, Ramis is survived by two sons, Julian and Daniel; a brother, Steve; and two grandchildren.

A private service is planned for this week. A public memorial in Chicago is being planned, probably for May.

mcaro@tribune.com

Twitter @MarkCaro