After organ transplantation, strategies for simplifying the therapeutic regimen may improve adherence and prevent acute organ rejection and/or late graft loss. The aim of the present study was to evaluate the safety and efficacy of conversion from a tacrolimus (TAC) twice daily (bid) formulation to a once daily (qd) formulation in a large cohort of adult liver transplantation (LT) patients. This retrospective, observational, single-center study included 394 LT patients with at least 6 months' posttransplant follow-up and no rejection episodes in the last 3 months. The conversion from a bid formulation to a qd formulation was based on a 1:1 ratio. The mean age at the time of conversion was 53 years (range = 18-72 years); 66% were men. The main indication for LT was alcoholic cirrhosis (41%). The mean conversion time after LT was 74 months (range = 6-218 months). The mean serum TAC trough level decreased after conversion (6.1 ± 5.6 ng/mL before conversion versus 4.9 ± 2.5 ng/mL after conversion, P < 0.05). After a mean follow-up of 24 months after conversion, 6 patients had converted to cyclosporine, 14 patients had stopped all calcineurin inhibitors, 16 patients had returned to TAC bid, and 358 patients were still on TAC qd. Acute rejection episodes were observed in 7 patients. In conclusion, the results of our experience indicate that the conversion from a TAC bid formulation to a qd formulation is a safe and effective strategy for the management of stable LT patients. Liver Transpl 19:529–533, 2013. © 2013 AASLD.