To examine the association between male circumcision and the risk of gonorrhoea, syphilis, HIV and high-risk (hr) human papillomavirus (HPV). We used data from a cross-sectional study conducted among 1902 men in Tanzania. Circumcision status was assessed at a clinical examination and history of gonorrhoea and syphilis was obtained from questionnaire data. Penile samples were tested for HPV using Hybrid Capture 2 and genotyped by the INNO-LiPA HPV Genotyping Extra test. Blood samples were tested for HIV. Using logistic regression the association between male circumcision and gonorrhoea, syphilis, HIV and hr HPV was assessed estimating odds ratios (ORs) and 95% confidence intervals (CIs). All analyses were adjusted for age and lifetime number of sexual partners. In the multivariable analysis, the odds of gonorrhoea were lower in circumcised men compared with uncircumcised men (OR = 0.52; 95% CI: 0.37–0.74). Likewise, the odds of HIV were considerably lower in circumcised men (OR = 0.42; 95% CI: 0.26–0.67). Furthermore, lower odds of hr HPV were seen in circumcised men compared with uncircumcised men, although not statistically significant (OR = 0.81; 95% CI: 0.56–1.17). Finally, the odds of HPV16 (OR = 0.48; 95% CI: 0.23–0.98) and multiple (≥2) hr HPV types (OR = 0.71; 95% CI: 0.44–1.12) were lower in circumcised men than in uncircumcised men. Circumcised men have a significantly lower risk of gonorrhoea, HIV and HPV16, compared with uncircumcised men.