Although poor psychological adjustment to organ transplantation appears to be a major contributor to reduced quality of life and increased physical morbidity, the prevalence and risk factors for psychiatric disorder have not been considered beyond the first 12-18 months after transplantation. The authors enrolled a representative sample of 191 heart transplant recipients in a prospective examination of the prevalence, clinical characteristics, and risk factors for DSM-III-R major depressive disorder (MDD), generalized anxiety disorder (GAD), associated adjustment disorders, and posttraumatic stress disorder related to transplant (PTSD-T) during the 3 years postsurgery. Survival analysis indicates that cumulative risks for disorder onset were MDD, 25.5%; adjustment disorders, 20.8% (17.7% with anxious mood); PTSD-T, 17.0%; and any assessed disorder, 38.3%. There was only one case of GAD. PTSD-T onset was limited almost exclusively to the first year posttransplant. Episodes of MDD (but not anxiety disorders) that occurred later posttransplant (8 to 36 months postsurgery) were more likely than early posttransplant episodes to be treated with psychotropic medications. For both MDD and anxiety disorders, later episodes were less likely to be precipitated by transplant-related stressors than other life stressors. Factors increasing cumulative risk for psychiatric disorder posttransplant included pretransplant psychiatric history, female gender, longer hospitalization, more impaired physical functional status, and lower social supports from caregiver and family in the perioperative period. Risk factors' effects were additive; the presence of an increasing number of risk factors bore a dose-response relationship to cumulative risk of disorder.