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Background: Tacrolimus trough levels (TTL) during the first weeks after liver transplantation (LT) have been related with long-term renal function and hepatocellular carcinoma recurrence. Nevertheless, the significance of trough levels of tacrolimus during the early post-transplant period for the long-term outcome is under debate., Aim: To evaluate the effect of TTL during the first month on the long-term outcomes after LT., Methods: One hundred fifty-five LT recipients treated de novo with once-daily tacrolimus were retrospectively studied. Patients with repeated LT or combined transplantation were excluded as well as those who presented renal dysfunction prior to transplantation and/or those who needed induction therapy. Patients were classified into 2 groups according to their mean TTL within the first month after transplantation: ≤ 10 ( n = 98) and > 10 ng/mL ( n = 57). Multivariate analyses were performed to assess risk factors for patient mortality., Results: Mean levels within the first month post-transplant were 7.4 ± 1.7 and 12.6 ± 2.2 ng/mL in the ≤ 10 and > 10 groups, respectively. Donor age was higher in the high TTL group 62.9 ± 16.8 years vs 45.7 ± 17.5 years ( P = 0.002) whilst mycophenolate-mofetil was more frequently used in the low TTL group 32.7% vs 15.8% ( P = 0.02). Recipient features were generally similar across groups. After a median follow-up of 52.8 mo (range 2.8-81.1), no significant differences were observed in: Mean estimated glomerular filtration rate ( P = 0.69), hepatocellular carcinoma recurrence ( P = 0.44), de novo tumors ( P = 0.77), new-onset diabetes ( P = 0.13), or biopsy-proven acute rejection rate (12.2% and 8.8%, respectively; P = 0.50). Eighteen patients died during the follow-up and were evenly distributed across groups ( P = 0.83). Five-year patient survival was 90.5% and 84.9%, respectively ( P = 0.44), while 5-year graft survival was 88.2% and 80.8%, respectively ( P = 0.42). Early TTL was not an independent factor for patient mortality in multivariate analyses., Conclusion: Differences in tacrolimus levels restricted to the first month after transplant did not result in significant differences in long-term outcomes of LT recipients., Competing Interests: Conflict-of-interest statement: MG is a member of advisory boards and has received honoraria from Astellas, Novartis and Chiesi. JB has received honoraria from Astellas and Novartis. AV has received honoraria from Astellas and Novartis. All other authors have no conflicts to declare., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)