High annual figures of sexually transmitted infections are diagnosed in the Netherlands despite significant efforts to control sexually transmitted infections. Herein, we analyse trends and determinants of sexually transmitted infection diagnoses, co-infections, and sexual risks among visitors of 26 sexually transmitted infection clinics between 2007 and 2011. We recorded increased positivity rates of sexually transmitted infection (chlamydia, syphilis, gonorrhoea, and/or HIV) in women and heterosexual men up to 12.6% and 13.4% in 2011, while rates in men having sex with men were stable but high (18.8%) through the documented years. Younger age, origin from Surinam/Antilles, history of previous sexually transmitted infection, multiple partners, or a previous notification are the identified risk factors for a sexually transmitted infection in this population. Known HIV-infected men (men having sex with men and heterosexuals) were at highest risk for co-infections (relative rate heterosexual men: 15.6; men having sex with men: 11.6). Sexually transmitted infection positivity rates remained high (men having sex with men) or increased over time (women and heterosexual men), a fact that highlights the importance of continuing sexually transmitted infection prevention. Most importantly, the very high sexually transmitted infection co-infection rates among HIV-positive men requires intensified sexually transmitted infection reduction strategies to put an end to the vicious circle of re-infection and spread of HIV and other sexually transmitted infections.