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To estimate the effect of alcohol consumption on HIV acquisition while appropriately accounting for confounding by time-varying risk factors.African–American injection drug users in the AIDS Link to Intravenous Experience cohort study. Participants were recruited and followed with semiannual visits in Baltimore, Maryland between 1988 and 2008.Marginal structural models were used to estimate the effect of alcohol consumption on HIV acquisition.At entry, 28% of 1525 participants were women with a median (quartiles) age of 37 (32–42) years and 10 (10–12) years of formal education. During follow-up, 155 participants acquired HIV and alcohol consumption was 24, 24, 26, 17, and 9% for 0, 1–5, 6–20, 21–50, and 51–140 drinks per week over the prior 2 years, respectively. In analyses accounting for sociodemographic factors, drug use, and sexual activity, hazard ratios for participants reporting 1–5, 6–20, 21–50, and 51–140 drinks per week in the prior 2 years compared to participants who reported 0 drinks per week were 1.09 (0.60–1.98), 1.18 (0.66–2.09), 1.66 (0.94–2.93), and 2.12 (1.15–3.90), respectively. A trend test indicated a dose–response relationship between alcohol consumption and HIV acquisition (P value for trend = 9.7 × 10−4).A dose–response relationship between alcohol consumption and subsequent HIV acquisition is indicated, independent of measured known risk factors.