BACKGROUND: Men-who-have-sex-with-men (MSM) are at high risk of HIV and sexually transmitted infection (STI) transmission. Asymptomatic STIs are common in MSM and remain undiagnosed and untreated where syndromic management is advocated. Untreated STIs could be contributing to high HIV rates. This study investigated symptomatic (SSTI) and asymptomatic STIs (ASTIs) in MSM in Cape Town. METHODS: MSM, 18 years and above, were enrolled into this study. Participants underwent clinical and microbiological screening for STIs. Urine, oro-pharyngeal and anal swab specimens were collected for STI analysis, and blood for HIV and syphilis screening. A psychosocial and sexual questionnaire was completed. STI specimens were analysed for Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) infection. RESULTS: 200 MSM were recruited with a median age of 32 years (IQR 26-39.5). Their median number of sex partners within the last year was 5 (IQR 2-20). 155/200 (78%) reported only male sex partners while 45/200 (23%) reported sex with men and women. 77/200 (39%) reported transactional sex. At enrolment, 88/200 (44%) were HIV positive and 8/112 (7%) initially HIV-negative participants seroconverted during the study. Overall, 47/200 (24%) screened positive for either NG or CT. There were 32 MSM (16%) infected with NG and 7 (3.5%) of these men had NG infections at two anatomical sites (39 NG positive results in total). Likewise, there were 23 MSM (12%) infected with CT and all these men had infections at only one site. Eight of the 47 men (17%) were infected with both NG and CT. ASTI was more common than SSTI irrespective of anatomical site, 38 /200 (19%) versus 9/200 (5%) respectively (p<0.001). The anus was most commonly affected, followed by the oro-pharynx and then urethra. Asymptomatic infection was associated with transgender identity (OR 4.09 CI 1.60-5.62), ≥5 male sex partners in the last year (OR 2.50 CI 1.16-5.62) and transactional sex (OR 2.33 CI 1.13-4.79) but not with HIV infection. CONCLUSIONS: Asymptomatic STI was common and would not have been detected using a syndromic management approach. Although molecular screening for NG/CT is costly, in our study only four MSM needed to be screened to detect one case. This supports dual NG/CT molecular screening for MSM, which, in the case of confirmed NG infections, may trigger further culture-based investigations to determine gonococcal antimicrobial susceptibility in the current era of multi-drug resistant gonorrhoea.