Ramis died yesterday of autoimmune inflammatory vasculitis, a rare disease that involves swelling of the blood vessels, his agent said.
The star found fame as bespectacled ghost-hunter Egon Spengler in the 'Ghostbusters' franchise in 1984. But he was also a talented writer and director, who co-wrote and directed 'Caddyshack', 'Animal House' and 'Analyze This'.
"His creativity, compassion, intelligence, humour and spirit will be missed by all who knew and loved him," said his family in a statement.
The actor had reportedly been quiet about his illness, which dated back to 2010.
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Born in Chicago to shop owner parents Ruth and Nathan, Ramis studied at Washington University in St Louis.
He started his career as a writer by penning arts stories for his local newspaper and editing Playboy magazine's "party jokes" section.
After leaving the magazine, he joined Chicago's renowned Second City improvised comedy troupe but said he realised his limitations as a performer after encountering John Belushi.
The actor-director-comedian's death was mourned by modern comedians and stars on Twitter.
Funnyman Tom Arnold said he was inspired by his work. "So sad about Harold Ramis. His work changed my life and inspired me and made me want to do what I do. Very nice man and a good neighbour too."
Billy Crystal, who starred in Ramis' 'Analyze This' and 'Analyze That', wrote, "Sad to hear my friend Harold Ramis passed away. A brilliant, funny, actor and director. A wonderful husband and dad. Big loss to us all."
Rashida Jones remembered the late actor as a "comedy legend" and "a lovely man" while Julianne Moore called him "exceptionally talented, exceptionally kind".