Once in a Lifetime was adapted as a film in 1932. Directed by Russell Mack, this version starred Jack Oakie as George, Aline MacMahon as May, and Russell Hopton as Jerry.

A made-for-television version was aired in 1988, as an episode of Great Performances on PBS. Directed by Robin Midgley and produced by Shaun Sutton, it starred Zoe Wanamaker as May.