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Although tacrolimus is the basis of most maintenance immunosuppression regimens for kidney transplantation, concerns about toxicity have made alternative agents, such as belatacept, attractive to clinicians. However, limited data exist to directly compare outcomes with belatacept-based regimens to tacrolimus.We performed a propensity score matched cohort study of adult kidney transplant recipients transplanted between May 1, 2001, and December 31, 2015, using national transplant registry data to compare patient and allograft survival in patients discharged from their index hospitalization on belatacept-based versus tacrolimus-based regimens.In the primary analysis, we found that belatacept was not associated with a statistically significant difference in risk of patient death (hazard ratio, 0.84; 95% confidence interval [CI], 0.61-1.15, P = 0.28) or allograft loss (hazard ratio, 0.83; 95% CI, 0.62-1.11; P = 0.20) despite an increased risk of acute rejection in the first year posttransplant (odds ratio, 3.12; 95% CI, 2.13-4.57; P < 0.001). These findings were confirmed in additional sensitivity analyses that accounted for use of belatacept in combination with tacrolimus, transplant center effects, and differing approaches to matching.Belatacept appears to have similar longitudinal risk of mortality and allograft failure compared with tacrolimus-based regimens. These data are encouraging but require confirmation in prospective randomized controlled trials.