OBJECTIVES: The costs associated with kidney transplantation are substantial, not only because of transplantation surgery but also due to the life-long need for immunosuppressive medication to prevent graft rejection. We analyzed the clinical and economic consequences of the use of the two baseline immunosuppressants, tacrolimus (Tac), and cyclosporin (CyA), currently administered in clinical practice. METHODS: A retrospective economic analysis was performed from a hospital perspective in Italy, Spain, and Germany. The analysis was conducted on the ITT-population comprising 557 patients from 7 European countries. Thus, the clinical and medical resource information for the pharmacoeconomic analysis was pooled multi-country data, the cost data was country specific. Costs were calculated on the actual resources used by each patient and assigned to the treatment group to which the patient was randomized. Direct medical resource use data was costed over 6 months post transplantation. A local health economist collected cost information from published sources and personal interviews with clinicians. Costs were collected on study drug, concomitant medication, hospitalization, dialysis, and rejection episodes. To explore the impact of any variability of costs, a one-way sensitivity analysis was conducted. RESULTS: Six months after transplantation, patient survival was 99.3% (Tac) and 98.5% (CyA), p = 0.366; graft survival was 94.6% (Tac) and 91.9% (CyA), p = 0.139. The incidence of acute graft rejection was 32.5% (Tac) and 51.3% (CyA), p <0.0001. Cost-minimization analysis revealed savings for tacrolimus (per patient) of Euro 583-1874 for surviving patients, and €781-2305 for patients with functioning grafts. Tacrolimus was cost-effective for patients with rejection-free grafts; savings per patient were €4627-9919. The tacrolimus group consistently had lower total costs than the cyclosporin group. The cost advantages for tacrolimus were a result of lower overall hospitalization costs and lower incidences of dialysis and graft rejection. A sensitivity analysis regarding the main cost drivers (hospitalization, study drug, and concomitant medication) generally confirmed the robustness of this finding in all 3 countries.