IntroductionPre-exposure prophylaxis (PrEP) is an HIV prevention strategy that can reduce the risk of HIV acquisition by more than 90% if taken consistently. Although South Africa has been implementing PrEP since 2016, initially for selected population groups before expanding access to more people, there is a dearth of research focused on PrEP among adolescent boys and young men (ABYM), despite them experiencing high rates of HIV infection. To address this gap, we compared PrEP initiation rates by service delivery points (SDPs) among ABYM in KwaZulu-Natal, South Africa.MethodsWe conducted a population-based prospective study in 22 SDPs from July 2021 to July 2022 in KwaZulu-Natal, South Africa. Sexually active ABYM aged 15–35 years who tested HIV negative were recruited at purposively selected PrEP SDPs (i.e., healthcare facilities, secondary schools and Technical Vocational Education and Training (TVET) colleges, and community-based youth zones). We collected baseline quantitative data from each participant using self-administered electronic questionnaires built into REDCap, including demographic information such as age, sex, employment status and level of education, as well as PrEP initiation outcomes. We extracted data from REDCap and exported it to Stata version 17.0 for analysis, and then eliminated discrepancies and removed duplicates. We described baseline characteristics using summary and descriptive statistics (median, interquartile range [IQR] and proportions) and reported PrEP initiation proportions overall and by SDPs.ResultsThe study included 1104 ABYM, with a median age of 24 years (interquartile range (IQR): 21–28)). Almost all participants were black African (n = 1090, 99%), with more than half aged 15–24 years (n = 603, 55%) and 45% (n = 501) aged 25–35 years. The majority (n = 963; 87%) had attained a secondary level of education. Overall PREP initiation rate among adolescent boys and young men was low: among 1078 participants who were eligible for PrEP, 13% (n = 141) were started on PrEP. Among the participants who were initiated on PrEP, over three quarters (78%, n = 58) were initiated from high schools, compared with community-based youth zones (40%, n = 37), TVET colleges (26%, n = 16) and healthcare facilities (4%, n = 30).ConclusionsThis study provided evidence suggesting that expanding PrEP services to non-traditional settings, such as high schools, TVET colleges, and community-based organizations, may have a potential to increase PrEP access among ABYM in South Africa.