Abstract Tacrolimus has proven to be superior to cyclosporine-Sandim-mune with regard to the prevention of acute rejections, but data comparing tacrolimus with Neoral are scarce. A total of 128 consecutive renal transplant recipients was studied. The patients were treated with Neoral-based (n= 74) or tacrolimus-based (n= 54) immuno-suppressive regimens. Survival analyses (Cox regression analysis) were performed on an intention-to-treat basis. Renal function and cardiovascular risk profile were analyzed by means of a repeated-measures analysis of variance (ANOVA) up to 12 months after transplantation. Immunological features were less favorable in the tacrolimus group. Two-year patient and graft survival were comparable. Acute-rejection-free survival was 82% in the tacrolimus group versus 40% in the Neoral group (p < 0.0001). The severity of the rejections (1997 Banff classification) was comparable (P= 0.43). Immunological graft loss (3.7% vs 12.2%, P= 0.02) and conversion because of rejection (0% vs 28.4%, p < 0.001) were less in the tacrolimus group. A higher proportion (68.5% vs 14.9%, p < 0.001) was successfully put on monotherapy. Creatinine clearance, proteinuria, and fractional uric acid clearance were similar. In the tacrolimus group mean blood pressure was comparable, but patients needed less antihypertensive drugs (p < 0.001) and, even with fewer patients on lipidlowering drugs, total cholesterol was lower (5.2 vs 6.0 mmol/l, P= 0.003). Treatment for post-transplant diabetes mellitus was 18.5% versus 10.8% (P= 0.22). In both groups, antidiabetic medication could be withdrawn for most patients. This study indicates that tacrolimus is superior to cyclosporine-Neoral in preventing acute rejection with comparable patient and graft survival rates. Because of a lower need for treatment of hypertension and hypercholesterolemia, the cardiovascular risk profile is more favorable. A considerable proportion of patients can be successfully weaned off co-medication and treated with tacrolimus monotherapy.