Background The intentional use of drugs to have sex-chemsex-among men who have sex with men (MSM) might contribute to the high sexually transmitted infections (STI) prevalence in this group. Limited data is available on chemsex outside major cities. The current study investigated the use of a wide variety of drugs during sex among MSM living outside major cities in the Netherlands and their associations with STI. Methods In 2018, 350 MSM were recruited at STI clinics and 250 MSM completed an online questionnaire. Questionnaire data were linked to clients' most recent STI laboratory test results. Chemsex was defined as using cocaine, crystal meth, designer drugs, GHB/GBL, ketamine, speed, or XTC/MDMA during sex in the preceding six months. The use of other drugs was also assessed. Determinants (chemsex, specific drugs, number of drugs, combining, and frequency) potentially associated with STI were assessed using multivariable logistic regression analyses adjusting for sociodemographic characteristics and sexual history. Results Chemsex was reported by 35% (95%CI: 29-41) of the 250 participants. XTC/MDMA (27%; 68/250) and GHB/GBL (26%; 64/250) were the most used drugs. STI positivity was 33% (29/87) in MSM engaging in chemsex and 12% (12/163) in MSM not engaging in chemsex (p<0.001). Half of MSM engaging in chemsex (45/87) used three of more different chemsex drugs; STI positivity in this group was 44% (20/45). The only factor independently associated with STI was the use of three or more chemsex drugs (aOR: 4.13, 95%CI: 1.77-9.62). Conclusion This study shows that chemsex is prevalent among MSM visiting the STI clinic outside major cities in the Netherlands, suggesting that health services in both urban and non-urban areas should be aware of and informed on chemsex. MSM who used multiple drugs are at particular risk for STI, indicating a special need for STI prevention and care in this group.