© 2016 Elsevier Inc. Objectives: We examined whether gender differences exist regarding stress, symptom distress, coping, adherence, and social support 5 years after heart transplantation. Background: Differences exist in health-related quality of life outcomes by gender after heart transplantation; women report poorer outcomes. Methods: Patients (. n = 210, female = 42), were from a prospective, multi-site, study of health-related quality of life long-term after heart transplantation. Patients completed self-report instruments 5 years after heart transplantation (mean = 4.98 ± 0.17 years after transplant). Statistical analyses included two-sample t-tests, Chi-square or Fisher's exact test, and multivariable modeling. Results: Women did not report more overall stress or symptom distress, but reported more difficulty adhering to the transplant regimen, yet more actual adherence than men. Women reported using more negative coping styles, but reported more satisfaction with social support. Conclusions: Gender differences exist regarding appraisal of stress, coping styles, and coping resources long-term after heart transplantation. These differences may guide tailoring therapy regarding stress, poor coping, and lack of resources.