Background and Objectives: Sexually transmitted diseases have been epidemiologically linked to a variety of high-risk behaviors, including substance abuse. However, the relationship between alcohol consumption and risk for specific STDs has not been explored previously. Goal of this Study: We hypothesized that alcohol use is a risk factor for STD acquisition. Methods: Cross-sectional analysis of enrollment visits in a prospective cohort study evaluating behavioral and biological risk factors for STD in an inner-city STD clinic population. Subjects were administered a comprehensive behavioral and questionnaire which included a detailed sexual history and evaluation for substance use. Alcohol users were classified as “frequent drinkers” (>2 times/week) and “infrequent” drinkers. Clinical exam included laboratory evaluation for syphilis, gonorrhea, chlamydia, and human immunodeficiency virus infection (HIV). Results: In 1990-1992, 1,145 patients were enrolled; 245 (21%) were “frequent” drinkers. “Frequent” drinkers were more likely in the past month to have had more than 2 sex partners (OR = 3.3; 95% confidence interval [95%CI1 2.4-4.7), and use cocaine or injecting drugs. Frequent drinkers were more likely to be diagnosed with HIV (OR = 2.5; 95%CI 1.6-4.0) and syphilis (OR = 1.74, 95%CI 1.1-2.8), but not with gonorrhea or chlamydia. Similar patterns were seen in cocaine and injecting drug users. In a multivariate analysis controlling for gender, syphilis, injecting drug, cocaine use, and sexual orientation, there was a borderline association between frequent alcohol use and HIV infection (OR = 1.63; 95%CI 0.95-2.8; P = .07). Conclusions: Alcohol is frequently used in individuals at risk for STD, and is associated with other risk variables for HIV infection. Use of multiple drugs, including alcohol, is common. Nevertheless, these data suggest that alcohol use may have an independent behavioral effect that would increase the risk for HIV infection. © 1994 American Sexually Transmitted Diseases Association.