Objective: Acamprosate has been reported to be cost-effective in maintaining abstinence in alcohol-dependent patients initiating psychosocial rehabilitation. This analysis updates earlier estimates of the economic benefits of such therapy. Methods: Estimated costs (2006 USA dollars) were compared over one year between patients assumed to receive acamprosate as an adjunct to psychosocial rehabilitation versus psychosocial rehabilitation alone. Costs included acamprosate therapy, psychosocial rehabilitation services, and alcohol-related hospitalizations and physician visits. Resource use estimates were obtained from a prospective open-label cohort study. The cost of acamprosate was based on average wholesale price, and an assumed standard 15% discount; all other unit costs were estimated using a large USA health care claims database. Results: The estimated cost of acamprosate therapy over one year was $652 per patient (mean duration of treatment, 180 days). Estimated costs of psychosocial rehabilitation services were similar in the two groups. Estimated costs of alcohol-related hospitalizations and physician visits, however, were $1059 lower per patient among those assumed to receive acamprosate. Accordingly, the estimated total 1-year cost of alcohol-related care was $407 lower per patient among those assumed to receive acamprosate plus psychosocial rehabilitation versus psychosocial rehabilitation alone. Conclusion: Overall costs of alcohol-related care may be substantially lower among alcohol-dependent patients receiving acamprosate plus psychosocial rehabilitation in comparison with psychosocial rehabilitation alone.