Immunosuppressant agents have greatly increased graft and overall survival in heart transplant patients, but some of these agents (e.g., calcineurin inhibitors [CNI] and corticosteroids) can also induce adverse events that may contribute to cardiac allograft vasculopathy (CAV) (e.g., nephrotoxicity and cytomegalovirus infection). The current trend is therefore toward CNI- and steroid-sparing regimes. This study reports on the initial clinical experience with Certican (everolimus), a novel proliferation signal inhibitor with immunosuppressant properties that has been shown to prevent or delay CAV. Seven de novo heart transplant patients were treated at our center. Patients received cyclosporine for microemulsion (CsA; Neoral), corticosteroids and fluvastatin in addition to everolimus. Mean everolimus blood trough levels were maintained within the target range of 3 to 8 ng/ml throughout the first 14 weeks post-transplant. CsA was initiated at a reduced dose, and by Weeks 8 to 14 the mean trough blood level was 187.7 ng/ml. The combination of everolimus and reduced-dose CsA was not associated with increased incidence of biopsy-proven acute rejection (BPAR). Two patients did experience BPAR, but only very mildly (ISHLT Grade 1A). The mean creatinine level pre-transplant was 1.5 mg/dl; this increased to 2.0 mg/dl at 2 weeks post-transplant, but returned to near baseline levels during Weeks 8 to 14 (1.66 mg/dl). Some patients had elevated blood lipids. Patients receiving everolimus should have lipid levels monitored on a regular basis. Everolimus may allow optimization of immunosuppressant regimens in de novo heart transplant patients so that adequate efficacy can be achieved with reduced CNI exposure, thereby protecting kidney function.