Background: Although studies have provided us with a cross-sectional analysis of long-term quality of life (QOL) after transplantation, relatively few longitudinal studies have been done that allow us to understand changes in QOL over time. The purposes of our study were to describe QOL over time and identify predictors of QOL longitudinally from 5 to 10 years after heart transplantation. Methods: All 555 subjects enrolled in this study completed booklets of questionnaires. These patients had a mean age of approximately 54 years (range 21 to 75 years) at time of transplant. Seventy-eight percent were men and 88% were white. Participants completed nine self-report QOL instruments for this study. Statistical analyses included frequencies, means ± standard deviations (plotted over time), Pearson correlation coefficients and multiple regression coupled with repeated measures. Results: At 5 to 10 years after heart transplantation, recipients reported high levels of satisfaction with overall QOL and with health-related QOL, which was stable over the 5-year period. Predictors of satisfaction with overall QOL (that individually accounted for 1% variance or more) were primarily psychosocial variables (overall model explaining 71% of variance), whereas predictors of satisfaction with QOL related to health and functioning (that also explained ≥1% variance) included symptom distress and physical function, as well as psychosocial variables (overall model explaining 72% of variance). Conclusions: At 5 to 10 years after heart transplantation, QOL remained positive and stable. Bio-psychosocial variables predicted satisfaction with overall QOL and health-related QOL. Understanding of these bio-psychosocial variables provides direction for the development of long-term therapeutic strategies after heart transplantation so that patients can have good post-transplant outcomes. © 2007 International Society for Heart and Lung Transplantation.