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To compare the risk of HIV and sexually transmitted diseases (STD) among homeless Muslim (circumcised) and Hindu (uncircumcised) men in Kolkata, India.Many observational studies and clinical trials in Africa have demonstrated that male circumcision provides protection against HIV acquisition, but there are sparse data on circumcision and HIV in India, which has the largest number of HIV cases in the world.Using a two-stage probability proportionate to size cluster design among homeless men aged 18–49 years in Kolkata, India, data were obtained on religion, behavioral risk factors, and HIV/STD prevalence, by administering an anonymous questionnaire. Rapid HIV tests and testing for syphilis were performed on blood, and urine samples were obtained to test for gonorrhea.The odds ratio for HIV among Muslims (circumcised) compared to Hindus (uncircumcised) was 0.43 (95% confidence interval 0.29–0.67). Despite Muslims having more partners and visits to commercial sex workers, the rates of syphilis and gonorrhea were similar. The results suggest that a biological effect of circumcision protects against HIV infection.The beneficial effect of circumcision should be communicated to high-risk groups, as well as to the general population.