Objectives: To examine risk factors for the development of squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in a cohort of heart transplant (HT) recipients and, in particular, to evaluate the role of the cumulative doses of different immunosuppressive drugs. Design: Prospective nonconcurrent study. Setting: A dermatology clinic at a university hospital. Patients: A total of 230 HT recipients 18 years or older at the time of transplantation with at least 3 years of follow-up. Main Outcome Measures: The risk of SCC and BCC in HT recipients and the relationship between development of SCC and BCC and cumulative doses of different immunosuppressive agents, controlling for other potential risk factors (age, sex, sunlight exposure, skin type, and presence of warts). Results: The cumulative immunosuppressive drug dose 3 years after transplantation (calculated by a weighted linear combination of azathioprine, cyclosporine, and corticosteroid cumulative doses ) was independently associated with an increased risk of developing SCC but not BCC. On multivariate analysis, patients receiving a WLC higher than the 75th percentile 3 years after HT had a 4 times higher risk of SCC than recipients of a WLC lower than the 50th percentile 3 years after HT (95%confidence interval, 1.4-11.4; P = .008). Other significant risk factors for SCC development were older age at transplantation and a greater occupational sunlight exposure. The risk of developing BCC was only associated with older age at transplantation and skin type II. Conclusions: The risk of SCC but not of BCC in HT recipients was related to the level of global immunosuppression rather than to 1 specific drug. The level of immunosuppression should be kept as low as possible consistent with survival and function of the transplanted organ. Objectives: To examine risk factors for the development of squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in a cohort of heart transplant (HT) recipients and, in particular, to evaluate the role of the cumulative doses of different immunosuppressive drugs Settings: A dermatology clinic at a university hospital. Patients: A total of 230 HT recipients 18 years or older at the time of transplantation with at least 3 years of follow-up. Main Outcome Measures: The risk of SCC and BCC in HT recipients and the relationship between development of SCC and BCC and cumulative doses of different immunosuppressive agents, controlling for other potential risk factors (age, sex, sunlight exposure, skin type, and presence of warts). cumulative immunosuppressive drug dose 3 years after transplantation (calculated by a weighted linear combination of azathioprine, cyclosporine, and corticosteroid cumulative doses) was independently asso ciated with an increased risk of developing SCC but not BCC. On multivariate analysis, patients receiving a WLC higher than the 75th percentile 3 years after HT had a 4 times higher risk of SCC than recipients of a WLC lower than the 50th percentile 3 years after HT (95% confidence interval, 1.4-11.4; P = .008). Other significant risk factors for SCC development were older age at transplantation and a greater occupational sunlight exposure. The risk of developing BCC was only associated with older age at transplantation and skin type II. Conclusions: The risk of SCC but not of BCC in HT recipients was related to the level of global immunosuppression rather than to 1 specific drug. The level of immunosuppression should be kept as low as possible consistent with survival and function of the transplanted organ.