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This study evaluated the cost-effectiveness of a smoking cessation and relapse-prevention program for hospitalized adult smokers from the perspective of an implementing hospital. It is an economic analysis of a two-group, controlled clinical trial in two acute care hospitals owned by a large group-model health maintenance organization. The intervention included a 20-minute bedside counseling session with an experienced health counselor, a 12-minute video, self-help materials, and one or two follow-up calls.Outcome measures were incremental cost (above usual care) per quit attributable to the intervention and incremental cost per discounted life-year saved attributable to the intervention.Cost of the research intervention was $159 per smoker, and incremental cost per incremental quit was $3,697. Incremental cost per incremental discounted life-year saved ranged between $1,691 and $7,444, much less than most other routine medical procedures. Replication scenarios suggest that, with realistic implementation assumptions, total intervention costs would decline significantly and incremental cost per incremental discounted life-year saved would be reduced by more than 90%, to approximately $380.Providing brief smoking cessation advice to hospitalized smokers is relatively inexpensive, cost-effective, and should become a part of the standard of inpatient care.