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Concerns have been raised about patients' failure to persist in alcohol treatment. We examined prescriptions for oral naltrexone in a large, nationally distributed treatment population to identify characteristics and health-care utilization patterns associated with persistence.Data from the 2000–2004 MarketScan® Commercial Claims and Encounters Database were used to identify patients with alcohol-related claims who were prescribed naltrexone.Analysis identified patient characteristics that predicted persistence with naltrexone (defined as having filled prescriptions for ≥80% of the 6-month treatment period) and its association to health-care utilization.Of 1138 patients, 162 (14.2%) were persistent in obtaining naltrexone. Non-persistent patients were significantly younger, more likely to be hourly employees and to live in an area with a lower median income, and less likely to be newly diagnosed with an alcohol-related disorder. Non-persistence in obtaining naltrexone was associated with significantly more intensive treatments, including inpatient detoxification, emergency room visits and hospitalizations.Over a 6-month period, 85.8% of patients who filled an initial prescription for naltrexone did not persist in obtaining the medication. Non-persistence was associated with significantly greater use of costly health-care services. Because the study was correlational, it is not possible to conclude that persistence reduced health-care costs, as patients with a better prognosis may have been more persistent. Research is needed to determine whether interventions that enhance persistence with naltrexone therapy improve treatment outcomes and reduce health-care costs.