BACKGROUND: Adolescents and young adults (AYA) make up a significant share of the world's burden of HIV and other sexually transmitted infections (STI). Self-testing can increase testing coverage and strengthen the uptake of prevention and treatment services. We critically appraised the literature regarding HIV, hepatitis, and syphilis self-testing among AYA (age 10-24 years) and assessed its usability, feasibility, and acceptability. METHODS: We conducted a systematic review, searching six databases between January 2010 and October 2023. We included all studies on HIV, hepatitis and syphilis self-testing in AYA. We used a random-effects meta-analysis to pool evidence across the three infections as evidence was deemed sufficiently similar. We summarised the uptake, proportion of first-time testers and linkage to care. Qualitative data were narratively synthesised. FINDINGS: We identified 89 relevant studies. Most were conducted in Africa (57/89, 64 %) and lower-middle-income countries (34/89, 38 %). Our meta-analysis of 27 studies (n = 28,787 individuals) demonstrated that 79 % (95 % CI: 69-87 %, I = 99 %) of AYA who were offered HIV or syphilis self-test completed the test. Five studies (n = 4117) demonstrated 62 % (95 % CI: 53-71 %, I = 83 %) were first-time testers. No studies reported completion rates for hepatitis self-testing. In general, AYA were highly accepting of self-testing and found it easy to use. INTERPRETATION: Self-testing is a safe, acceptable and effective way to increase access to HIV, hepatitis and syphilis testing in AYA. Given these features of self-testing, policies to increase its use should significantly improve testing and maximise their public health impact.