The original Broadway production, directed by Edward Royce, opened on November 18, 1919 at the Vanderbilt Theatre, where it ran for 675 performances, at the time the record for the longest-running show in Broadway history, one it maintained for nearly two decades. The cast included Edith Day as Irene, Walter Regan as tycoon Donald Marshall, Eva Puck as Helen Cheston, Gladys Miller as Jane Gilmour, and Bobby Watson as 'Madame Lucy', a flamboyant male dress designer. The show made a star of Day, who departed the cast after five months to recreate her role at London's Empire Theatre, where it ran for 399 performances. Day was replaced in the Broadway production by Helen Shipman.
Irene enjoyed a brief Broadway revival at Jolson's 59th Street Theatre in 1923 with Dale Winter as Irene, Jere Delaney as Madame Lucy, and Walter Regan reprising his role as Donald. Eventually there were 17 national touring companies, and it was filmed twice, first as a 1926 silent movie with Colleen Moore and again in 1940 with Anna Neagle.