Active on the stage in both his native Boston and New York, Guilfoyle was part of an informal repertory company who appeared on Broadway and in Boston supporting actor Al Pacino in such productions as "The Training of Pavlo Hummel", "Richard III" and "Man and Superman". After making his feature debut in one of the biggest flops of the 1980s, "Howard the Duck" (1986), Guilfoyle was cast in supporting roles in such features as "Beverly Hills Cop II" (1987), "Mrs. Doubtfire" (1993), and "Quiz Show" (1994).
Guilfoyle is not to be confused with character actor Paul Guilfoyle (1902-61), who appeared in films during the 1930s, 40s and 50s.