This study sampled 445 sexually active women, 18 and older, from 52 shelters that serve people who are homeless in Los Angeles county and used event-based analyses to examine how alcohol and drug use are associated with protected sex among these women. Data were collected through individual computer-assisted face-to-face structured interviews. Both between-subjects analyses (n = 445) and within-subjects analyses (n = 87) were used to examine the association between substance use and protected sex. In both within- and between-subjects analyses, women who drank alcohol before sex were significantly more likely to engage in protected sex compared with women who did not drink alcohol. However, there was no association between women's drug use, or their male partner's alcohol or drug use, and whether they engaged in protected sex. The higher likelihood of protected sex during events when women drank alcohol could be explained by partner choice (both analyses) and discussing condom use before sex (within-subjects analyses only). The findings of this study challenge the common belief that women's alcohol use before sex increases the likelihood of risky sexual behavior, but are consistent with several previous studies suggesting that alcohol use may be associated with protected sex under certain conditions. Results from this study highlight the need to better understand the complexities of how alcohol use may influence the sexual behavior of impoverished women.