Many patients attempt to stop smoking during hospitalization, but most relapse after discharge. This study developed and evaluated a brief smoking-cessation and relapse-prevention program for hospitalized smokers. All hospitalized smokers (n = 1,119) were identified by questionnaire at hospital admission and then received either usual care or usual care plus a hospital-based smoking-cessation intervention regardless of interest in stopping smoking. Intervention components included a 20-minute bedside counseling session, a 12-minute videotape, a variety of self-help materials, and a follow-up telephone call. Special attention was given to techniques for preventing relapse after hospital discharge. Defining ex-smokers as those who reported no tobacco use at both 3- and 12-month follow-up assessments, and counting those lost to follow-up as smokers, the intervention increased the proportion of patients who quit smoking by one half (9.2% vs 13.5%, P < 0.05). These results demonstrate the efficacy of a brief in-hospital intervention and suggest that relapse-prevention efforts are needed to convert temporary cessation during hospitalization into long-term abstinence.