Introduction: Little is known about the effect of posttransplant opioid use on adherence to immunosuppressant therapy (IST) among adult renal transplant recipients (RTRs). Objective: The aim of this study was to examine the relationship between opioid use and IST adherence among adult RTRs during the first year posttransplant. Methods: Longitudinal data were analyzed from a retrospective cohort study examining US veterans undergoing renal transplant from October 1, 2007, through March 31, 2015. Data were collected from the US Renal Data System, Centers for Medicare and Medicaid Services Data (Medicare Part D), and Veterans Affairs pharmacy records. Dose of opioid prescriptions was collected and divided based on annual morphine milligram equivalent within a year of transplant. Proportion of days covered of greater than or equal to 80% indicated adherence to tacrolimus. Unadjusted and multivariable-adjusted logistic regression analyses were performed. Results: A study population of 1,229 RTRs included 258 with no opioid use, while 971 opioid users were identified within the first year after transplantation. Compared to RTRs without opioid usage, RTRs with opioid usage had a lower probability of being adherent to tacrolimus in unadjusted logistic regression (odds ratio [OR] (95% confidence interval [CI]): 0.22 [0.07–0.72]) and adjusted logistic regression (OR [95% CI]: 0.11 [0.03–0.44]). These patterns generally remained consistent in unadjusted and adjusted main and sensitivity analyses. Conclusions: Findings indicate RTRs who use prescription opioids during the first year posttransplant, regardless of the dosage/amount, are less likely to be adherent to tacrolimus. Future studies are needed to better understand underlying causes of the association between opioid use and tacrolimus nonadherence.