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The study objective was to determine the association between immunosuppressant therapy (IST) adherence and graft failure among pediatric renal transplant recipients (RTRs) using data reported in the United States Renal Data System (USRDS), which contains Medicare prescription claims. RTRs (≤18 years) who received their only transplant during 1995–2000, experienced graft survival more than 6 months posttransplant, had 36 months of USRDS data (or had data until graft failure or death), utilized Medicare IST coverage, and were prescribed cyclosporine/tacrolimus were included. IST adherence was measured by medication possession ratio (MPR). Cox proportional hazards analysis was used to assess the relationship between time to graft failure and continuous MPR. MPR quartiles were used to examine MPR as a categorical variable (Quartile 4 = adherent group, Quartiles 1–3 = nonadherent group). Kaplan-Meier estimates of time to graft failure were compared between adherent and nonadherent groups. 877 RTRs met inclusion criteria. Cox proportional hazards modeling suggested that greater adherence was significantly associated with longer time to graft failure (p = 0.009), after adjusting for relevant clinical factors. Kaplan-Meier analysis found a difference between adherent and nonadherent groups in graft survival by time (χ2 = 5.68, p = 0.017). Interventions promoting adherence should be implemented among pediatric RTRs and parents/guardians to optimize graft survival.