To determine the impact of treatment with oral naltrexone on healthcare costs in patients with alcohol-related disorders. Using data from the MarketScan Commercial Claims and Encounters Database for 2000-2004, we identified a naltrexone group (with an alcohol-related diagnosis and at least one pharmacy claim for oral naltrexone) and two control groups. Alcohol controls had an alcohol-related diagnosis and were not prescribed an alcoholism treatment medication. Nonalcohol controls had no alcohol-related diagnosis and no prescription for an alcoholism treatment medication. The control groups were matched three to one to the naltrexone group on demographic and other relevant measures. Healthcare expenditures were calculated for the 6-month periods before and after the index naltrexone drug claim (or matched date for controls). Univariate and multivariate analyses were used to compare the groups on key characteristics and on healthcare costs. Naltrexone patients (n = 1,138; 62% men; mean age 45 +/- 11 years) had significantly higher total healthcare expenditures in the pre-index period than either of the control groups. In the postindex period, naltrexone patients had a significantly smaller increase than alcohol controls in total alcohol-related expenditures. Total nonalcohol-related expenditures also increased significantly less for the naltrexone group than for the alcohol control group. Multivariate analyses showed that naltrexone treatment significantly reduced alcohol-related, nonalcohol-related, and total healthcare costs relative to alcohol controls. Although prior to treatment patients with alcohol-related disorders had higher healthcare costs, treatment with oral naltrexone was associated with reductions both in alcohol-related and nonalcohol-related healthcare costs.