Background: In the HIV/AIDS pandemic, the perinatally HIV-infected children, who are surviving to adolescence, constitute a particular group, with specific needs to manage HIV disease and to prepare their future. Adolescents living with perinatal HIV (ALPHIV) often experience difficult living circumstances that can impact educational achievement and thus, insertion in the adult life. We explore the school trajectories of ALPHIV and determine the relative contribution of HIV-infection and the contextual environment to their schooling situations.Methods: We used data from the Teens Living With Antiretrovirals (TEEWA) study, a cross-sectional case-control study, conducted from 2011 to 2014 in Thailand. We analysed data for 707 ALPHIV (cases) aged 12–19 years, receiving antiretroviral therapy in 20 hospitals throughout Thailand and 689 HIV-uninfected adolescents (controls) living in the same institutions or, for those living in family settings, randomly selected in the general population and individually matched for sex, age and residence. Schooling disruption was defined as ≥1 year academic delay or early school dropout. Logistic regression was used to assess factors independently associated with schooling disruption and to estimate the attributable fraction of school disruption related to HIV-infection. We used multivariate imputations by chained equations to manage missing data and we performed two sensitivity analyses to evaluate the reliability of our main model.Results: ALPHIV were 5 times more likely to experience schooling disruption than controls after adjustment on sociodemographic factors ( ORA=5.2 [3.7-7.2]). About 50% of schooling disruption could be attributed to HIV-infection. Boys and adolescents living in institutions were more likely to experience schooling disruption (ORA =1.8 [1.3-2.4] and ORA =11.0 [7.7-15.8], respectively). Among ALPHIV, mental and growth delays were significantly associated with schooling disruption (ORA =3.3 [2.1-5.2] and =1.8 [1.3-2.6], respectively). For ALPHIV living in family, schooling disruption was also associated with stigmatization experiences (ORA =1.9 [1.2-3.1]) and caregiver’s low education (ORA =2.1 [1.1-3.9]). Conclusions: HIV and contextual factors combine to aggravate ALPHIV educational disadvantage. Further research is needed to clarify the pathways leading to a disrupted school trajectory among ALPHIV. The impact of this educational disadvantage on their life prospects, especially regarding access to higher education and professional achievement, should be explored in future research.