Irrera went to college in Florida, attending Barry University and St. Thomas University.
Irrera has appeared on The Oprah Winfrey Show, The View, The Tonight Show Starring Johnny Carson in 1986, The Tonight Show with Jay Leno, The Late Late Show with Craig Ferguson, and The Late Show with David Letterman.
Irrera is a regular performer at the Cat Laughs in Kilkenny; he has made 22 appearances at the festival, more than any other comic. He appeared on an episode of the NBC sitcom Seinfeld as Ronnie Kaye, the prop comic and on the CBS sitcom The King of Queens as Spero Demopolous. Irrera made 11 appearances as himself on the animated series Dr. Katz, Professional Therapist, and is the only comic to appear in all six seasons.[citation needed]

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