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.