Background: A multivariate approach to the study of relationships between quality of life and demographic, physical, and psychosocial variables after heart transplantation has not been examined in a large, multi-site sample. The purpose of this study was to describe quality of life, examine relationships between quality of life and demographic, physical, and psychosocial variables, and identify predictors of quality of life in patients who were 1 year post heart transplantation. Methods: Data were collected from a nonrandom sample of adult patients (n = 232) who were 1 year post heart transplantation at a Midwestern or Southern medical center. Nine self-administered instruments and chart review were used to gather data from patients. All tools had adequate psychometric support. Descriptive statistics, Pearson correlations, and step-wise multiple regression were used to analyze data. Level of significance was set at 0.05. Results: Patients were most satisfied with the areas of quality of life regarding social interaction and least satisfied with their psychological state. Patients experienced an average amount of stress, were coping fairly well, reported overall good quality of life, and were very satisfied with the outcome of their transplant surgery. Nine out of 16 variables were significant predictors of quality of life and explained 66% of the variance in quality of life: less stress, more helpfulness of information from health care providers, better health perception, better compliance with the transplant regimen, more effective coping, less functional disability, less symptom distress, older age, and fewer complications. Conclusions: Predictors of quality of life at 1 year after heart transplantation were primarily psychological. Additional variance in quality of life was explained by physical, somatic sensation, demographic, and health status variables. Knowledge of these factors provides (1) information to identify patients who are at risk for poor quality of life at 1 year after heart transplantation and (2) direction for the development of interventions to improve quality of life.