BackgroundMen who have sex with men (MSM) who practice chemsex have a higher likelihood of engaging in risky sexual behaviors and higher rates of HIV infection and other sexually transmitted infections (STIs) than those who do not. ObjectiveThis trial aimed to evaluate the effectiveness of a web-based intervention in reducing the sexual harms of chemsex among MSM. MethodsThe study was a 2-arm, assessor-blinded, randomized, parallel-group trial with a 3-month follow-up period. The study was conducted in the year 2021 in Hong Kong. Underpinned by the theory of planned behaviors and a harm reduction approach, the intervention consisted of interactive components and knowledge-based information about chemsex. Participants in the control group received brief information and content about sexual violence. The primary outcome was self-efficacy in refusing risky sexual behaviors and chemsex, as measured by the Condom Self-Efficacy Scale (CSES), Self-Efficacy for Sexual Safety (SESS) instrument, and Drug Avoidance Self-Efficacy Scale (DASES). The secondary outcomes included intentions to have chemsex, actual engagement in chemsex, HIV and other STI testing, and condom use in the last 3 months. All outcomes were self-reported. An online structured questionnaire was used to collect data. ResultsIn total, 316 MSM enrolled in the study. The intervention group demonstrated a significantly larger improvement in condom-use self-efficacy (as measured by CSES scores; time-by-group interaction: β=4.52, 95% CI 2.03-7.02; P