*Purpose: Evidence regarding the efficacy of maintenance immunosuppression (IS) regimens for liver transplantation (LT) arise from clinical trials. However, the ‘real world’ effectiveness of such medication practices has not been studied on a population level.

*Methods: This is a retrospective cohort study of the association of maintenance IS and the combined outcome of death or retransplantation (reLT) using national data from the United Network for Organ Sharing. IS regimens included: calcineurin inhibitor (CNI) with anti-metabolite (antiM) and steroids, CNI with antiM, CNI with steroids, CNI alone and other. Maintenance regimen was assessed at discharge, 6 months, 1 year and 2 years from LT. Each Cox proportional hazard model was adjusted for regimens received at prior time points, induction IS, pre-LT clinical and demographic characteristics, and used center as a shared frailty term. CNI alone was the reference group in all models.

*Results: The most commonly used regimens were CNI+antiM at 6 months and 1 year post-LT (30.3% and 33.94%, respectively), and CNI alone at 2 years post-LT (38.8%). CNI+antiM at 6 months was associated with a significantly reduced adjusted hazard ratio (aHR) for death/reLT compared to all other regimens (Table; aHR 0.79, 95% CI: 0.73-0.86). At 1 year post-LT, the adjusted risk of death/reLT was lowest with using either CNI+antiM or CNI alone (aHR 0.92, 95% CI: 0.83-1.03), however at 2 years post-LT CNI+antiM was again associated with the lowest risk of death/reLT (aHR 0.84, 95% CI: 0.71-0.99).

*Conclusions: In conclusion, two-drug therapy with CNI+antiM up to 2 years post-LT was associated with the lowest risk of death/reLT. Despite the potential for over-IS, these findings support the proposed benefits of CNI-minimization using combination therapy with an antiM among LT recipients at large.

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