OBJECTIVES: We tested the efficacy of a combined pharmacologic and behavioral smoking cessation intervention among women in a state prison in the southern United States. METHODS: The study design was a randomized controlled trial with a 6-month waitlist control group. The intervention was a 10-week group intervention combined with nicotine replacement therapy. Two hundred and fifty participants received the intervention, and 289 were in the control group. Assessments occurred at baseline; end of treatment; 3, 6, and 12 months after treatment; and at weekly sessions for participants in the intervention group. RESULTS: The intervention was efficacious compared with the waitlist control group. Point prevalence quit rates for the intervention group were 18% at end of treatment, 17% at 3-month follow-up, 14% at 6-month follow-up, and 12% at 12-month follow-up, quit rates that are consistent with outcomes from community smoking-cessation interventions. CONCLUSIONS: Female prisoners are interested in smoking cessation interventions and achieved point-prevalence quit rates similar to community samples. Augmenting tobacco control policies in prison with smoking cessation interventions has the potential to address a significant public health need.