The safety and tolerability of everolimus has been evaluated in a randomized, phase II trial, comparing 3 doses of everolimus to a placebo, in association with cyclosporine and corticosteroids, after liver transplantation. There were no significant differences between groups in the rates of the composite end point (graft failure, biopsy-proven acute rejection, graft loss, death, or loss to follow-up) or its individual components. Although there were lower rates of treated acute rejection and mortality with the higher dosages (2 and 4 mg/day), these did not reach statistical significance. Interestingly, freedom from rejection correlated with trough blood levels of everolimus: patients with levels of 3 ng/mL or less had rejection rates 3-fold higher than patients with levels exceeding 3 ng/mL. All graft losses and most deaths were associated with typical posttransplant complications, not with study medication and not due to hepatic artery thrombosis. There were no clear dose-related differences among groups for hematology parameters. After transplantation, renal function declined to a similar extent in all 4 groups. The overall incidence of infection was comparable between groups (61-77%). Although the interpretation of the results of this trial is hampered by the small sample sizes of patient groups (about 30 in each group) and the high dropout rates (about 50%), this study suggests that everolimus is an effective immunosuppressive agent with an acceptable patient tolerance and safety profile after liver transplantation.