The production was directed by Philip Seymour Hoffman for the LAByrinth Theatre Company and moved to the Union Square in March. It concerns a group of former schoolmates who are reunited at the funeral of the strict nun who had taught them. The production stars Elizabeth Canavan, Liza Colon-Zayas, Melissa Feldman, Mark Hammer, Ron Cephas Jones, Russell G. Jones, John Ortiz, Richard Petrocelli, Portia, Al Roffe, Felix Solis, and David Zayas.
In his review of the production for TheaterMania, Dan Bacalzo wrote: "Our Lady of 121st Street should not be missed. Guirgis's script is full of passion and humor, Hoffman keeps the action moving at a nearly relentless pace, and you'd be hard pressed to find a more consistent, emotionally daring cast."