Objectives: In a sample of patients undergoing procedural deep sedation in the emergency department (ED), we conducted a prospective, randomized, single-blinded trial of audio-therapy for smoking cessation. Methods: We asked subjects about their smoking, including desire to quit (0-10 numerical scale) and number of cigarettes smoked per day. Subjects were randomized to either a control tape (music alone) or a tape with repeated smoking-cessation messages over music. Tapes were started with first doses of sedation and stopped with patient arousal. Telephone follow-up occurred between two weeks and three months to assess the number of cigarettes smoked per day. Study endpoints were self-reported complete cessation and decrease of half or more in total cigarettes smoked per day. Results: One hundred eleven patients were enrolled in the study, 54 to intervention and 57 to control. Mean desire to quit was 7.15 ± 2.6 and mean cigarettes per day was 17.5 ± 12.1. We successfully contacted 69 (62%) patients. Twenty-seven percent of intervention and 26% of control patients quit (mean difference = 1%; 95% CI: –22.0% to 18.8%). Thirty-seven percent of intervention and 51% of control patients decreased smoking by half or more (mean difference = 14.6%; 95% CI: –8.7% to 35.6%). Conclusion: Suggestive audio-therapy delivered during deep sedation in the ED did not significantly decrease self-reported smoking behavior.