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Aasif was born in Bombay, Maharashtra, India. He moved to Bradford, West Yorkshire, England, UK, when he was 1 year old and lived in Bradford until he was 16 years old. He then moved to Tampa, Florida, USA, when he was 16 years old.

He and Connie Britton used to perform together in a Murder Mystery company.

Graduated from the University of South Florida, where he majored in theater.

His one-man show "Sakina's Restaurant" was the first play written by a South Asian American to be produced Off Broadway.

In November 2014, he published his first book, "No Land's Man," a collection of personal essays.

Ismail Merchant cast Mandvi as the lead in the film The Mystic Masseur (2001) after seeing him perform "Sakina's Restaurant," his one-man show.

During his first-ever appearance on The Daily Show (1996), Bruce Springsteen was in the studio audience.