Objective: To examine the incidence, tumor burden, and risk factors for nonmelanoma and other skin cancer types in this heart transplant cohort. Design: Retrospective review of patient medical records. Setting: Tertiary care center. Patients: All heart transplant recipients at Mayo Clinic from 1988 to 2006. Main Outcome Measures: Cumulative incidence of skin cancer and tumor burden, with Cox proportional hazards regression models used to evaluate risk factors for posttransplant primary and secondary nonmelanoma skin cancer. Results: In total, 312 heart transplant patients had 1395 new skin cancers in 2097 person-years (mean, 0.43 per year per patient) with a range of 0 to 306 for squamous cell carcinoma (SCC) and 0 to 17 for basal cell carcinoma (BCC). The cumulative incidence rates of any skin cancer were 20.4%, 37.5%, and 46.4% at 5, 10, and 15 years after heart transplant, respectively. Cumulative incidence of SCC after the first BCC was 98.1% within 7 years. Multivariate analysis showed that posttransplant nonskin cancer, increased age, and heart failure etiologic factors other than idiopathic disease were associated with increased risk of SCC. Posttransplant herpes simplex viral infection, increased age, and use of mycophenolate mofetil for immunosuppression were associated with increased risk of BCC. Conclusions: With prolonged survival, many heart transplant patients have numerous skin cancers. Vigilant sun protection practices, skin cancer education, and regular skin examination are appropriate interventions in these high-risk patients. ©2009 American Medical Association. All rights reserved.