Antidepressants are of demonstrated value in short-term treatment of functional chest pain, but long-term outcome data are unavailable. Follow-up information over a median of 2.7 years (0.8-8.6 years) was systematically obtained from 21 outpatients treated with tricyclic antidepressants after incomplete response to antireflux therapy. Initial treatment produced at least moderate symptom reduction or remission in 17 subjects (81.0%). Of these, 7 (41.2%) were successfully treated continuously or for symptom relapses over an average of 2.6 years; 5 (29.4%) discontinued successful treatment after >0.5 years with sustained benefits; and 5 (29.4%) eventually discontinued treatment because of side effects or for uncertain reasons (1 having a sustained remission). Low-dose tricyclic antidepressants were considered the most effective long-term chest pain treatment significantly more often than were antireflux medications or calcium-channel blockers in this selected patient group (P<0.05 for each). We conclude from this retrospective review that fully three fourths of subjects with functional chest pain who initially respond to open-label treatment with low-dose tricyclic antidepressants will use them continuously or for symptom relapses over at least the next two to three years and consider them the most effective treatment for their symptoms.