Drug use before or during sex is a high-risk sexual behavior associated with adverse health risks and outcomes, such as increasing the likelihood of overdoses and of acquiring sexually-transmitted diseases. This systematic review and meta-analysis of three scientific databases examined the prevalence of the use of intoxicating substances, those tending to excite or stupefy the user on a psychoactive level, before or during sex, among young adults (18–29 years old). A total of 55 unique empirical studies met the inclusion criteria (48,145 individuals; 39% males), were assessed for risk of bias using the tools of Hoy et al. (2012), and were analyzed via a generalized linear mixed-effects model. The results produced a global mean prevalence of this sexual risk behavior of 36.98% (95% CI: 28.28%, 46.63%). Nonetheless, significant differences were identified between different intoxicating substances, with the use of alcohol (35.10%; 95% CI: 27.68%, 43.31%), marijuana (27.80%; 95% CI: 18.24%, 39.92%), and ecstasy (20.90%; 95% CI: 14.34%, 29.45%) significantly more prevalent than that of cocaine (4.32%; 95% CI: 3.64%, 5.11%), heroin (.67%; 95% CI: .09%, 4.65%), methamphetamine (7.10%; 95% CI: 4.57%, 10.88%), and GHB (6.55%; 95% CI: 4.21%, 10.05%). Moderator analyses showed that the prevalence of alcohol use before or during sex differed according to geographical sample origin, and increased as the proportion of ethnic whites in samples increased. The remaining demographic (e.g., gender, age, reference population), sexual (e.g., sexual orientation, sexual activity), health (e.g., drug consumption, STI/STD status), methodological (e.g., sampling technique), and measurement (e.g., timeframe) variables that were examined did not moderate prevalence estimates. Implications for sexual development interventions were discussed.