Objective: It is not known if parental psychiatric disorders have an independent effect on offspring smoking after controlling for genetic and environmental vulnerability to nicotine dependence. We tested if parental alcohol, drug, or conduct disorders; antisocial personality disorder; depression; and anxiety disorders remained significant predictors of offspring smoking initiation, regular smoking, and nicotine dependence before and after adjusting for genetic and environmental risk for nicotine dependence. Method: Data were obtained via semistructured interviews with 1,107 twin fathers, 1,919 offspring between the ages of 12 and 32, and 1,023 mothers. Genetic and environmental liability for smoking outcomes was defined by paternal and maternal nicotine dependence. Multinomial logistic regression models were computed to estimate the risk for offspring trying cigarettes, regular smoking, and the Fagerström Test for Nicotine Dependence (FTND) as a function of parental psychopathology and sociodemographics before and after adjusting for genetic and environmental vulnerability to nicotine dependence. Results: Before adjusting for genetic and environmental risk for nicotine dependence, ever trying cigarettes was associated with maternal depression, regular smoking was associated with maternal alcohol dependence and maternal conduct disorder, and FTND was associated with paternal and maternal conduct disorder and antisocial personality disorder. No parental psychopathology remained significantly associated with regular smoking and FTND after adjusting for genetic and environmental vulnerability to nicotine dependence in a multivariate model. Conclusions: The association between parental psychopathology and offspring smoking outcomes is partly explained by genetic and environmental risk for nicotine dependence. Point estimates suggest a trend for an association between parental antisocial personality disorder and offspring regular smoking and nicotine dependence after adjusting for genetic and environmental vulnerability. Studies in larger samples are warranted.