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Men who have sex with men (MSM) are more likely to use drugs and other substances compared to their heterosexual peers. No studies have evaluated patterns of substance use among MSM adults in Mexico. We used latent class analysis (LCA) to identify MSM subgroups with specific substance use patterns and their associations with sexual behaviors., Methods: Data from 1850 adult MSM were collected at HIV clinics in Mexico City between September 2018 and December 2019. The structural equation modeling approach was used to estimate a LC model to identify patterns of substance use by self-report of substance use (i.e., cigarette smoking, alcohol, and drugs). To evaluate LC membership, we included HIV status, condomless anal sex (CAS), and serosorting, while controlling for demographic variables., Results: 30.3% were under the age of 22. Alcohol use in last 30 days (76.2%), binge drinking (29.2%), marijuana (29.4%), sex-drugs (23.9%), stimulants (13.7%), and depressants (6.3%). MSM reported engaging in CAS (55.9%) and serosorting (13.5%) behaviors, and 40% reported being HIV positive. LCA indicated three general categories of MSM substance users: Class 1 (49.0%), Class 2 (29.8%), and Class 3 (20.4%). Members of Class 3 were younger: 23-28 age years (aOR = 1.86) and 29-33 age years (aOR = 1.86), more educated: completed graduate studies (aOR = 1.60), had a high probability of polysubstance use and were more likely to engage in CAS and serosorting., Conclusions: Attempts to detect alcohol and problematic use of substances are needed for MSM followed by culturally competent approaches that address alcohol and drug use disorders.