Sexualized drug use (SDU) to enhance and extend sexual relations may involve risks of substances abuse (intoxication, interactions and overdose) and higher exposure to HIV and other sexually transmitted infections. There are inconsistencies in the methodology and findings of previous research on SDU in Latin America (LA), and more studies are required. The purpose of this research was to characterize SDU in gay men and other men who have sex with men from 18 LA countries, and describe the aspects by comparing people who practice and do not practice SDU, at the general and country levels. Cross-sectional study based on the data collected by LAMIS-2018. Dependent variable was SDU (last 12 months), and the independent variables were: drug use (in any context/in sexual context), sociodemographic, socioepidemiological, and psychosocial aspects. A descriptive analysis was carried out, comparing those who practiced and did not practice SDU. LAMIS-2018 included 64,655 participants, averaging 30 years of age. 13.6% declared having practiced SDU (6.6% with multiple partners). In the last sexual encounter the most commonly used drugs were cannabis (9.3%), poppers (6%), and Viagra (5.4%), and in the last encounter with multiple partners, poppers (19.7%), cannabis (17%), and Viagra (13.2%). HIV diagnosis was reported by 27% of people practicing SDU, vs. 14.3% in the other group. Severe anxiety-depression symptoms were more common among people practicing SDU (9.2% vs. 7%), as were the episodes of homophobic intimidation (52.6% vs. 48.2%), insults (34.4% vs. 28.6%), and aggression (4.1% vs. 3.0%). SDU was reported by a high percentage of people, with a predominance of the use of drugs related to sexual practice, and others for recreational use. Aspects described as the higher proportion of self-reported HIV diagnosis and severe symptoms of anxiety-depression among those who practiced SDU, show that is necessary to implement preventive strategies to reduce the harmful impacts that can sometimes result from this practice, including harm reduction policies, promote access to mental health services and support in situations of homophobia and stigma.