Introduction: Smoking is a well-established correlate of suicidal behavior. It is not known if familial risk factors contribute to this association. Methods: Data were obtained via semistructured interviews with 1,107 twin fathers, 1,919 offspring between ages 12-32 years, and 1,023 mothers. Familial vulnerability to nicotine dependence and suicidal behavior was modeled via father and maternal self-report of these behaviors. Multinomial logistic regression models were computed with and without familial risk factors to estimate the association between offspring ever smoking, regular smoking, nicotine dependence, and a 4-level offspring suicide variable: (a) none, (b) ideation, (c) ideation + plan, and (d) ideation + plan + attempt or ideation + attempt. All models were stratified by gender and adjusted for sociodemographics, familial risk factors including parental suicidal behavior, nicotine dependence, and conduct disorder, and offspring conduct disorder, depression, alcohol abuse/dependence, and illicit drug abuse/dependence. Results: After adjusting for covariates and familial risk factors, ever smoking was not significantly associated with suicidal behavior in males and females. In males, regular smoking was associated with ideation + plan (odds ratio [OR] = 5.47; 95% CI: 1.05-28.60), and in females, regular smoking was associated with ideation + plan + attempt or ideation + attempt. In both genders, nicotine-dependent smoking was associated with ideation + plan + attempt or ideation + attempt (males: OR = 6.59; 95% CI: 1.91-22.70, females: OR = 3.37; 95% CI: 1.25-9.04). Comparison of models with and without familial risk factors indicated that there is no mediation of smoking status and suicidal behavior by familial risk. Conclusions: Smoking and nicotine dependence are correlated with suicidal behaviour. Contributions from familial risk factors did not significantly alter this association.