Early preview audiences were so confused by the ending of A Letter to Three Wives that there were public debates over which of the three husbands ran off with Addie Ross, and General Douglas MacArthur had an aide write director Joseph L. Mankiewicz for clarification. Mankiewicz explained the plot to the New York Times, then quipped, "The people who've been doing the wondering don't believe what they hear in the picture." People still speculate that Jeanne Crain's absent husband really did run off with Addie, but Paul Douglas' character lied to soften the blow and bring problems with his wife (Linda Darnell) to a head.

20th Century-Fox attempted to capitalize on the film's popularity by re-teaming Darnell and Douglas later that year in Everybody Does It. The comedy about a society woman attempting to break into opera only to discover her husband has the real voice was not as successful. At one point, Douglas sees a nursing cat and quips, "A litter from three wives."

The 1951 comedy Three Husbands was intended as a sequel to A Letter to Three Wives. Writer Vera Caspary, who had collaborated on the earlier film's screenplay, initially called it A Letter to Three Husbands. When it moved from 20th Century-Fox to an independent production company, the connection was lost. The film told of three husbands who receive a letter from a recently deceased friend in which he claims to have had affairs with each man's wife. It starred Eve Arden, Ruth Warrick, Howard Da Silva, Shepperd Strudwick and Billie Burke.

Darnell and Douglas reprised their roles in A Letter to Three Wives on Lux Radio Theatre in 1950 and on Screen Players Guild in 1949 and 1952.

When A Letter to Three Wives first appeared on television, Kirk Douglas' diatribe against radio and advertising was cut by many stations for fear of offending their sponsors.

NBC presented a movie-of-the-week remake of the film in 1985, with Loni Anderson in Darnell's role, Michele Lee taking over for Ann Sothern and Stephanie Zimbalist as Crain's young innocent. Sothern also appeared, but as Anderson's mother. She had been offered Thelma Ritter's role as the maid, but said she couldn't carry a dinner tray. The small part paid off when British director Lindsay Anderson saw the film and cast her opposite Bette Davis, Lillian Gish and Vincent Price in The Whales of August (1987), the film that brought her only Oscar® nomination.

A 2010 episode of The Simpsons titled "Moe Letter Blues" borrows the plot of A Letter to Three Wives.

by Frank Miller