Sirolimus is used in patients with renal insufficiency after liver transplantation (LT) and especially in those with calcineurin inhibitor (CNI)-associated nephrotoxicity. We conducted a systematic review of all randomized controlled trials and observational studies to test the hypothesis that the use of sirolimus is associated with an improvement in renal function at 1 year in LT recipients with renal insufficiency [glomerular filtration rate (GFR) < 60 mL/minute or creatinine level โก 1.5 mg/dL]. We performed a search of all major databases, conference proceedings, and relevant journals through December 2009 and contacted content experts, corresponding authors, and the pharmaceutical manufacturer. A random effects model was used to determine the pooled estimate of the change in renal function and pooled risk estimates of adverse events that may be associated with sirolimus-based therapy at 1 year. Eleven studies (three randomized controlled trials and eight observational studies) met the final inclusion criteria. A nonsignificant improvement of 3.38 mL/minute [95% confidence interval (CI) 5 22.93 to 9.69] was observed in methodologically sound observational studies and controlled trials reporting the primary outcome. In controlled trials, baseline GFR >50 mL/min sirolimus use was associated with an improvement of 10.35 mL/ minute (95% CI 5 3.98-16.77) in GFR or creatinine clearance. Sirolimus was not significantly associated with death [relative risk (RR) 5 1.12, 95% CI 5 0.66-1.88] or graft failure (RR 5 0.80, 95% CI 5 0.45-1.41), although reporting was incomplete. It was associated with a statistically significant risk of infection (RR 5 2.47, 95% CI 5 1.14-5.36), rash (RR 5 7.57, 95% CI 5 1.75-32.70), ulcers (RR 5 7.44, 95% CI 5 2.03-27.28), and discontinuation of therapy (RR 5 3.61, 95% CI 5 1.32-9.89). Conclusion: Conversion to sirolimus from CNIs is associated with a nonsignificant improvement in renal function in LT recipients with renal insufficiency, although the results are limited by heterogeneity, a risk of bias, and a lack of standardized reporting. (HEPATOLOGY 2010;52:1360-1370) R enal insufficiency in liver transplantation (LT) recipients is associated with progression to end-stage renal disease and a decrease in patient and graft survival. After LT, calcineurin inhibitors (CNIs) contribute further to the develop-ment of chronic renal failure. Minimizing the nephrotoxicity of immunosuppressive regimens may help to reduce the number of patients developing chronic renal failure and its associated morbidity and mortality after LT.