Like individuals exposed to other life stressors, patients undergoing organ transplantation typically show elevated psychological distress initially post-transplant, with improvement thereafter. However, this 'average' pattern may conceal subgroups with differing profiles of psychological response. We sought to identify unique temporal distress profiles, and their predictors, after heart transplantation. A total of 156 transplant recipients (refusal rate, 6%) were enrolled and assessed at 2, 7, 12, 36, and 42 months post-transplant. Cluster analysis was used to identify distinct distress profiles over time. Multivariate analyses examined health and psychosocial predictors of the profiles. Five groups were identified, with either: (a) low distress at all time-points (45% of the sample), (b) high, clinically significant distress at all times (21%), (c) high distress over several years with low distress only at final assessment (12%), (d) high distress during the first several months with decline thereafter (6%), or (e) fluctuating distress levels (16%). Patients showing any distress (versus none) were more likely to have a pre-transplant psychiatric history, poorer social supports and more physical impairment early post-transplant, and continued physical impairment over time. Among distressed patients, those with persistent (versus declining) distress were most likely to be female, waited more briefly for transplant, and were most physically impaired early post-transplant. While persistently distressed patients had better social supports early post-transplant, these supports subsequently worsened. Individuals differ in whether and when psychological distress abates after heart transplantation. Findings regarding distress profiles and their predictors may inform the design of interventions to address each transplant recipient's unique psychological needs.