Background: Men who have sex with men (MSM) are disproportionally affected by sexually transmitted infections (STI). STI are often extragenital and asymptomatic. Both can delay diagnosis and treatment. HIV-positive (HIV+) MSM often show higher STI-prevalence than HIV-negative MSM (HIV-). Approval of HIV pre-exposure prophylaxis (PrEP) might have influenced sexual behaviour and STI-prevalence of HIV- MSM. We estimated STI-prevalence and risk factors amongst HIV- and HIV+ MSM in Germany to plan effective interventions. Methods: We conducted a nationwide, cross-sectional study between 2/2018-7/2018. Thirteen MSM-friendly STI-practices screened MSM for Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Neisseria gonorrhea (NG), and Trichomonas vaginalis (TV) using self-collected rectal and pharyngeal swabs, and urine samples. APTIMATM STI-assays (HologicTM Inc., San Diego, USA) were used for diagnostics, and samples were not pooled. We collected information on socio-demographics, HIV-status, clinical symptoms, sexual behaviour within the last 6 months, and PrEP-use. We combined HIV status and PrEP use for defining risk groups, and used multivariate logistic regression to identify risk factors for STI. Results: 2,303 MSM were included: 50.5% HIV+, median age 39 [18-79] years. Median number of male sex partners within the last six months was 5. Unprotected anal intercourse (active and/or passive, UAI) was reported by 73.2%, 43.5% use of party drugs. 78.9% had a STI history, 32.1% of STI+ MSM reported STI-related symptoms. 27.6% of HIV- MSM used PrEP. Overall STI-prevalence was 30,1%, and 25.0% in HIV-/PrEP- MSM (CT:7.2%; MG:14.2%; NG:7.4%; TV:0%), 40.3% in HIV-/PrEP+ MSM (CT:13.8%; MG:19.4%; NG:14.8%; TV:0.4%), and 30.8% in HIV+ MSM (CT:10.1%; MG:18.4%; NG:8.6%; TV:0.1%). Independent risk factors were HIV/PrEP-status (HIV-/PrEP+ OR:1.4; 95%-CI:1.0-2.0; HIV+ OR:1.5; 95%-CI:1.1-1.9), >5 sex partners (OR:1.5; 95%-CI:1.2-1.9), UAI (OR:1.9; 95%-CI:1.5-2.6), and use of party drugs (OR:1.5; 95%-CI:1.2-2.0). Conclusions: We found a high STI-prevalence in MSM in Germany, especially in PrEP users, frequently being asymptomatic. Higher STI prevalence in PrEP users than in HIV+ MSM was partly explained by differences in risk behaviour. As a relevant proportion of PrEP users will not use a condom, counselling and comprehensive STI screening is essential and should be low threshold and preferably free of cost. Counselling of PrEP users should also address use of party drugs.