This study sought to estimate rates of adherence to nucleoside reverse transcriptase inhibitors (NRTIs) during the first year of administration in the California Medicaid (Medi-Cal) population. A retrospective analysis of pharmacy claims data regarding NRTI prescription refills was employed to estimate adherence and persistence with therapy throughout 1 year in treatment-naive individuals. Adherence was defined as the proportion of days on which drugs were taken during the first 365 days of therapy, and persistence was assessed according to whether prescriptions were refilled over time within a tolerable threshold (60 days). A total of 2614 men and 1174 women exhibited a mean overall adherence rate of 53.0%, and 35.6% of individuals were persistent with therapy throughout the year. No differences in persistence or adherence rates by sex were detected (P =.30). The proportion of individuals with adherence of 80% or better was 26%. Age was found to be significant in adherence and persistence by chi-square examination (P =.001). We conclude that nonadherence can be a critical issue during the first year following initiation of therapy. Comprehensive adherence support programs may be required to maximize adherence, especially among subjects aged 18-24 years, and should be made available early in the course of therapy, or before it is initiated.