Alcohol and drug use disorders are highly comorbid with tobacco use. Given the substantial health risks associated with concurrent substance use and smoking, there is a clinical need to identify factors that confer heightened risk for their cause. This investigation examined gender-specific associations between smoking behaviors with current alcohol and drug use diagnoses. Data were derived from the National Epidemiologic Survey on Alcohol and Related Conditions (N = 42,565). Relationships between smoking status and DSM-IV current alcohol and drug use diagnoses by gender were assessed in terms of odds ratios using regressions. The presence of current alcohol or drug diagnoses increased the odds of being a daily, occasional, or former smoker, and gender was found to moderate these associations. Overall, women with a current alcohol use disorder had greater odds of being a daily or occasional smoker compared with men (odds ratio [OR], 3.52 versus 2.93; 5.22 versus 3.56). Women with a drug use diagnosis had greater odds of being a daily smoker compared with men (OR, 6.54 versus 4.63) and similar odds of being an occasional smoker (OR, 4.48 versus 4.51). The results of this study highlight gender-specific patterns of comorbidity, which may contribute to more focused primary and secondary prevention efforts.