The differences between sexualized drug use (SDU), the use of any psychoactive substance in sex, and chemsex, the use of crystal methamphetamine, mephedrone, or gamma-hydroxybutyrate/gamma-butyrolactone in a sexual context under a specific mindset among gay, bi and other men who have sex with men (GBMSM), have not yet been empirically investigated. The purpose of this study is to examine the differences between SDU and chemsex in regards to demographics, sexual health, and psychosocial variables. For this purpose, 215 GBMSM reporting SDU filled out an online questionnaire. It investigated HIV status, diagnoses of Sexually Transmitted Infections (STIs), condom use, Post Exposure Prophylaxis, Pre-Exposure Prophylaxis, frequency of substance use, polydrug use, and percentage and enjoyment of sober sexual activity. Compared to other forms of SDU, chemsex was more frequently related to living in large urban areas, positive HIV status, STI diagnoses, condomless sex, a higher number of sexual partners, polydrug use, disinhibition in sex, lower sober sex enjoyment, and sober sexual life percentage. Place of residence, polydrug use, and the number of partners remained significant in the multivariable analysis. Chemsex should also be addressed as a distinct practice by affirmative, properly trained in sexual health and harm reduction healthcare professionals.