On Broadway she appeared in Frankenstein (1981), directed by Tom Moore, portrayed Desdemona in Othello (1982) opposite James Earl Jones and Christopher Plummer and co-starred with John Lithgow in Christopher Durang's romantic screwball comedy Beyond Therapy (1982), directed by John Madden. (She played opposite Lithgow again in the Herbert Ross film Footloose. During the 1980s, she also performed in Hedda Gabler, directed by Lloyd Richards at Yale Repertory Theatre, and in Harold Pinter's A Kind of Alaska (1984, Manhattan Theatre Club), Lanford Wilson's Serenading Louie (1984), and Janusz Glowacki's Hunting Cockroaches (1987, Manhattan Theater Club). As Wiest became established as a film Actress through her work in Woody Allen's films, she was less frequently available for stage roles. However, she did appear onstage during the 1990s, in In the Summer House, Square One, Cynthia Ozick's The Shawl, and Naomi Wallace's One Flea Spare. In 2003, she appeared with Al Pacino and Marisa Tomei in Oscar Wilde's Salome. In 2005, she starred in Kathleen Tolan's Memory House. She also starred in a production of Wendy Wasserstein's final play Third (directed by Daniel Sullivan) at Lincoln Center.