BACKGROUND: Prioritizing HIV prevention for adolescent girls and young women (AGYW) at high risk of HIV acquisition in sub-Saharan Africa (typically considered ≥3 per 100 person years [PYs]) is urgently needed, but identifying these AGYW is challenging. We sought to assess and, if needed, enhance a risk assessment tool from the VOICE trial for identifying AGYW at high risk for HIV in Lilongwe, Malawi. METHODS: A multisite prospective cohort study was conducted among sexually active AGYW 15–24 years old at four health centers in 2016–2017. The VOICE tool was first applied and then updated by excluding variables that were not predictive and adding variables that were. Incidence rates (IR), incidence rate ratios (IRR), ninety-five percent confidence intervals (CIs), area under the receiver-operator characteristic curve (AUC), sensitivity, and specificity were calculated. RESULTS: Seven-hundred ninety-five participants experienced 14 seroconversions over 672 person-years (IR: 2.08 per 100 PYs, CI: 1.23–3.52). The VOICE tool had moderate predictive ability (AUC: 0.64, CI: 0.52, 0.75). Maintaining two variables (genital ulcers and vaginal discharge), removing five socio-demographic variables, and adding two variables (ever pregnant and >5 year male-female age gap) enhanced performance (AUC=0.79, 95% CI: 0.69–0.89). Thirty-five percent had a score of 0, 41% had a score of 1–2, and 24% had a score ≥3. A score ≥1 resulted in 100% sensitivity, 35.9% specificity, and an IR of 3.25 per 100 PYs. A score ≥3 resulted in 64.3% sensitivity, 76.8% specificity, and an IR of 5.89 per 100 PYs. CONCLUSIONS: A simple risk assessment tool identified a subset of AGYW in Malawi at high risk of HIV acquisition who may benefit from biomedical HIV prevention.