To analyze the factors that increase the practice of condomless anal sex (CAS) among adolescent men who have sex with men (AMSM) and adolescent travestis and transgender women (ATGW) in three Brazilian state capitals. PrEP1519 is a prospective, multicenter cohort study demonstrating the effectiveness of human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) among AMSM and ATGW aged from 15 to 19 years in three Brazilian state capitals. The analyses were performed with baseline cohort data, including 1,418 adolescents enrolled from 2019 to 2021. The outcome studied was CAS in the last six months, and the potentially associated factors were sociodemographic, behavioral, healthcare, and history of violence and discrimination. Descriptive, bivariate, and multivariate analyses were conducted. Adjusted prevalence ratios (aPRs) and 95% confidence intervals (95%CI) were estimated. Most of the participants were AMSM (91.5%), aged 18 to 19 years (75.9%), Black (40.5%), with secondary or higher education in progress (92.7%), with CAS during the first sexual intercourse (54.2%), sexual initiation before the age of 14 (43.4%), and history of group sex (24.6%) and transactional sex (14.6%). The prevalence of CAS in the last six months was 80.6% (95%CI 78.5%-82.6%). Adolescents who reported condomless first sexual intercourse (aPR: 1.18; 95%CI 1.10-1.25), use of psychoactive substances (aPR: 1.09; 95%CI 1.03-1.16), and transactional sex (aPR: 1.11; 95%CI 1.04-1.20) had a higher prevalence of CAS in the last six months. We also found that those aged 15 to 17 years had a higher prevalence of CAS than those aged 18 to 19 (aPR: 1.07; 95%CI 0.99-1.13). The prevalence of CAS was high among AMSM and ATGW, being associated with practices that may increase the risk of sexually transmitted infections (STIs). Therefore, it is recommended to strengthen sexual health programs for young people that address the issue of sexuality and STI prevention, as well as to expand access to preventive methods, such as condoms and PrEP.