The purpose of this study was to test the effectiveness of a multi-component smoking cessation intervention in African American women residing in public housing. The intervention consisted of: (a) nurse led behavioral/empowerment counseling; (b) nicotine replacement therapy; and, (c) community health workers to enhance smoking self-efficacy, social support, and spiritual well-being. The results showed a 6-month continuous smoking abstinence of 27.5% and 5.7% in the intervention and comparison groups. Changes in social support and smoking self-efficacy over time predicted smoking abstinence, and self-efficacy mediated 6-month smoking abstinence outcomes. Spiritual well-being did not predict or mediate smoking abstinence outcomes. These findings support the use of a nurse/community health worker model to deliver culturally tailored behavioral interventions with marginalized communities.