The purpose of this study was to determine the significance and patient profiles of nonadherence with immunosuppressive therapy in the etiology of late acute rejections (LARs), more than 1 year after heart transplantation. Nonadherence was assessed in 101 heart transplant recipients (14 females, 87 males) with a median age of 56 (Q1 = 50; Q3 = 61) and a median posttransplant status of 3 (range, 1-6) years, using electronic event monitoring and self-report. The influence of depression, perceived self-efficacy, knowledge, perceived health, symptom frequency and distress, perceived social support, and adherence with outpatient appointments on medication nonadherence was examined. Ten LARs occurring in six patients were observed. Nine of the rejections, emerging in five patients, appeared to be caused by medication nonadherence. Nonadherence with immunosuppressive therapy is a major risk factor in the etiology of LAR. Patient profiles allow the identification of patients at risk.