This gender-specific research study compares the relative effectiveness of two theory-based interventions targeting women who smoke. Women with coronary artery disease (CAD; n = 53) or CAD risk factors (n = 107) were randomly assigned to either coping-skills Relapse Prevention (RP) treatment or an educational/ supportive treatment based on Health Belief Model (HBM) principles. RP was comparable, but not superior to HBM treatment, as indicated by the lack of differential smoking outcomes at 3 and 6 months. RP was more effective than HBM for women with low self-efficacy, as predicted. The presence of a smoking-related disease had a substantial effect on smoking status, in that the odds of being abstinent at 6 months were 2.2 times greater for non-diagnosed women when compared with CAD women. These findings indicate that more potent relapse prevention interventions are needed to increase cessation rates in women who smoke, especially those with established heart disease.