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Objectives: In sub-Saharan Africa, approximately 86% of HIV infections in adolescents aged 15-19 years occur among girls. Their heightened susceptibility is likely influenced by converging sociobehavioural and biological factors, although the relative contributions remain unclear. To address this, we compared known and hypothesised risk factors for HIV between cisgender adolescent girls and adult women in South Africa and evaluated the relationships between these factors and sexually transmitted infection (STI) status., Methods: This cross-sectional observational study included adolescent (n=305; 14-19 years) and adult females (n=114; 25-35 years) in two South African provinces (Western Cape (WC), KwaZulu-Natal (KZN)). Demographic and sociobehavioural data were collected by questionnaire. Colposcopy was conducted to identify cervicovaginal abnormalities, and tests for bacterial vaginosis (BV), Chlamydia trachomatis , Neisseria gonorrhoeae and Trichomonas vaginalis were performed., Results: Adults reported higher risk sexual behaviour than adolescents across multiple variables, although adolescents were more likely to have STIs than adults (62.8% vs 34.0%, respectively, p=0.0010 for WC; 42.5% vs 16.4%, respectively, p=0.0002 for KZN). Adolescents did, however, report earlier sexual debut (16 years old vs 17 years old, p<0.0001 for both sites) and KZN adolescents were more likely to use intravaginal sexual enhancers than adults (34.6% vs 20.6%, respectively, p=0.0417). Numbers of sexual partners (β-coefficient: 0.34, SE: 0.12, p=0.0054) and sex acts within the previous 3 months (β-coefficient: 0.25, SE: 0.09, p=0.0062) were associated with STIs in adolescents and trended to significance for adults. Intravaginal sexual enhancer use (KZN only; β-coefficient: 0.95, SE: 0.38, p=0.0118) and biological risk factors, including BV Nugent score (β-coefficient: 0.09, SE: 0.04, p=0.0257) and signs of cervicovaginal injury/inflammation (β-coefficient: 1.07, SE: 0.45, p=0.0171), were associated with STIs in adolescents but not adults., Conclusions: Risk factors for STIs including HIV may differ between age groups of girls and women, and mitigation interventions may need to be tailored accordingly., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)