The objective of this study was to compare the prevalence of substance use and alcohol-related consequences among bisexual and heterosexual women. A cross-sectional survey was self-administered to a random sample of undergraduate women. The final sample consisted of 49 self-identified bisexual women and 2,042 self-identified heterosexual women. Bivariate and multivariate results indicated that bisexual women were more likely than heterosexual women to report cigarette smoking, illicit drug use and medically prescribed use of antidepressant prescription medication. Although their drinking behaviors were similar, bisexual women were more likely than heterosexual women to experience adverse alcohol-related consequences. These findings suggest that traditional-age undergraduate women who self-identify as bisexual may be at heightened risk for substance use. However, additional research is needed to replicate these findings with larger samples of bisexual women.