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To assess human immunodeficiency virus (HIV), syphilis, and behavioral risk factors among men who have sex with men (MSM) in southwestern China, where HIV started as a drug-driven epidemic, and shifted to mainly heterosexual transmission.These cross-sectional studies were conducted yearly in 2013, 2014, and 2015 in Guangxi, China. A total of 1,996, 1,965, and 1,697 participants were recruited in 2013, 2014, and 2015, respectively. The data included demographic and sexual behavioral variables. Other variables included individuals who used illegal drugs, and who received HIV counseling, testing, and free condoms, and peer education. Participants were tested for HIV, syphilis, and hepatitis C virus (HCV) with whole blood specimens. Questionnaires and laboratory testing data were double entered, and validated with EpiData software. The data were then transferred into SPSS software (SPSS Inc, Chicago, IL) and Chi-square test performed.The prevalence of HIV was 6.6% in 2013, 8.4% in 2014, and 11.2% in 2015. The prevalence of syphilis was 9.3% in 2013, 9.8% in 2014, and 6.1% in 2015. And HCV prevalence was 0.5% in 2013 and remained stable at 0.4% in 2014, and 2015. HIV infection, and associated factors among MSM in these 3 annual cross-sectional survey showed that HIV-infected MSM were significantly, more likely, to perform unprotected anal intercourse with any commercial male partners in the past 6 months (adjusted odds ratio [AOR] = 1.81, 95% CI: 1.50–2.20), had sex with any female partners in the past 6 months (AOR = 1.31, 95% CI: 1.01–1.71), used drugs in the past (AOR = 2.73, 95% CI: 1.30–5.71), and are syphilis infected (AOR = 3.53, 95% CI: 2.77–4.49).There is an urgent need for intervention strategies like condom distribution, HIV counseling, free testing, and education regarding safe sex, HIV, and other sex-related diseases in Guangxi to curb, and prevent HIV among MSM.