Background: This study examined the association between social, demographic, and psychologic factors and smoking status among Appalachian Ohio women. A secondary aim examined whether specific factors could be identified and segmented for future tailored treatment of tobacco dependence. Methods: A cross-sectional survey (n = 570) obtained information about social, demographic, and psychologic factors and smoking. Logistic regression described associations between these characteristics and smoking status. Chi-square automatic interaction detection (CHAID) analyses identified subgroups at risk for smoking. Results: Fifty-two percent never smoked, with 20.5% and 27.5% categorized as former and current smokers, respectively. Women with low adult socioeconomic position (SEP) were more likely to smoke (odds ratio [OR] 3.05, 95% confidence interval [CI] 1.74-5.34) compared to high SEP women. Other factors associated with current smoking included age 31-50 (OR 2.30, 95% CI 1.22-4.33), age 18-30 (OR 3.29, 95% CI 1.72-5.34), Center for Epidemiologic Studies Depression scale (CES-D) score ‡ 16 (OR 1.99, 95% CI 1.31-3.05), and first pregnancy at age < 20 (OR 1.74, 95% CI 1.14-2.66). The prevalence of smoking was 50% among those with four or more risk factors compared to 10% for those reporting no risk factors. CHAID analyses identified low adult SEP and depressive symptoms as the combination of risk factors most strongly associated with smoking; 49.3% of women in this subgroup currently smoked. Conclusions: Low SEP in adulthood, maternal circumstances, and depressive symptoms are associated with current smoking. Tailored cessation interventions that address these risk factors should be developed and further evaluated in an attempt to reduce disparities in smoking prevalence among this vulnerable group of women.