INTRODUCTION: Sirolimus (SRL) has been used as an alternative to calcineurin inhibitors (CI) to spare renal function in liver transplant (LT) recipients. SRL received a black-box warning in LT because of concerns about hepatic artery thrombosis (HAT). Prior to this, we initiated a large number of LT patients on SRL. This study assesses the long-term safety of SRL in LT recipients. METHODS: This is a retrospective, single-center study of all LT recipients who initiated SRL from 2001-2006. A group that remained on SRL was compared to a group that discontinued SRL for adverse events (CNI group). Groups were compared for demographics, and LT outcomes. Kaplan-Meier analyses with Cox regression models were done to determine risk factors (RF), including SRL use, for death or end-stage renal disease (ESRD). RESULTS: 159 patients were included. 109 (68.5%) remained on SRL and 50 (31.4%) discontinued (CNI). There were no differences between groups in age at transplant, gender, race, etiology of liver disease or time after LT to SRL initiation. In SRL vs. CNI, there were no differences in HAT (2.8 vs. 2.0%), CAD (6.4 vs. 10%) or CVA (5.7% vs. 11.9%) (Table 1). Fewer patients on SRL died (47.7% vs. 58.0%) or developed ESRD (19.3 vs. 32.0%) though neither difference was significant at P = 0.228 and P = 0.078. No significant differences were noted in GFR between the two groups up to 10 years after LT. In the evaluation of risk factors to time to ESRD, CNI (SRL discontinuation) trended towards earlier onset of ESRD on univariate analysis (HR: 1.56, CI: 0.78, 3.23, P = 0.207 but not on multivariate analysis (HR:1.366, CI:0.675–2.763) (Figure 1). In the evaluation of RF for time of death, CNI was associated with greater mortality from time of transplant (HR: 1.46, CI: 1.06–2.03, P = 0.023) and from time of SRL initiation (HR: 1.64, CI: 1.06–2.55, P = 0.026). However, when including age, diabetes and GFR at LT in a multivariate analysis, the effect of CNI was no longer significant. CONCLUSION: The results describe one of the longest follow-up periods for SRL use in LT patients including 35 patients followed for over a decade. The results demonstrate that patients receiving SRL after LT did not have an increased risk of developing diabetes, CAD, CVA or HAT. Furthermore, SRL was at least equivalent to CNI in terms of ESRD and mortality. This suggests that SRL, in appropriate LT patients, is safe and that LT patients currently receiving SRL can continue to do so.Table 1.: showing baseline demographic variables and clinical characteristicsFigure 1.: Overall survival between groups from time of SRL conversion. End of SRL used as time varying variable.Figure 2.: Overall survival between groups from time of SRL conversion. End of SRL used as time varying variable.