Abstract Background Some male heterosexual clients prefer to visit a cross-border Female Sex Worker (FSW) because of cheaper sex and unsafe sex practices, and may therefore be at risk for sexually transmitted infections (STI). The objective of this study was to assess whether having commercial cross-border sex is an independent risk factor for being diagnosed with a STI. Methods An observational retrospective study was performed using data of 8 Dutch STI clinics bordering Germany, between 2011 and 2013. All male heterosexual clients of FSWs were selected and data on country of FSW visit and occurrence of STI were used for multivariable regression analysis. Results The study population consisted of 2664 clients of FSW. Most clients visited the Netherlands (82.4%), followed by visits to another country (beyond cross-border) (9.9%) and cross-border visits (7.8%). Clients of FSW were less likely to be STI positive when they were younger than 25 years(OR = 0.6, 95%CI 0.4 to 0.8 25–44 years and OR = 0.5, 95%CI 0.4 to 0.7 older than 45 years), and more likely when they had 20 or more sex partners in the last 6 months (OR = 2.9, 95%CI 1.9 to 4.4), did not use a condom during last sexual contact (OR = 2.2, 95%CI 1.6 to 2.9) and made cross-border visits (OR = 1.7, 95%CI 1.1 to 2.6). Conclusions As cross-border visits appears to be a novel independent risk factor for STI in clients of FSW, this group should therefore be advised on STI prevention.