Background: The study was undertaken to assess the relative contributions of genetic and environmental influences on drunk-driving. Methods: Driving records of a cohort of male and female twins (N = 17,360) from the Mid-Atlantic Twin Registry were examined. Structural equation models were used to estimate the magnitude of genetic and environmental effects on male and female phenotypes, and test for gender differences. Results: There were significant gender and age effects. Compared with females, males were five times more likely to engage in driving under the influence. Among persons aged 21–49 years, the risk for drunk-driving was eight times that for those aged 50+ years and five times greater than those ≤20 years. In both males and females, aged 21–49 years, a large proportion (57%) of the variance in drunk-driving was due to genetic factors and the remaining 43% due to individual specific environmental influences. Conclusions: Drunk-driving is under significant genetic influence in both males and females. Our findings suggest that a different set of genes influence DUIs in men and women.