OBJECTIVE: Adolescent girls and young women (AGYW) have a much higher risk of HIV infection than young men of the same age. One hypothesis for this disparity is AGYW are more likely to be in sexual partnerships with older men with HIV; however, evidence has been inconclusive. DESIGN: We used longitudinal data from a randomized trial in South Africa (HPTN 068) to determined whether partner age difference is associated with incident HIV infection in AGYW. METHODS: Age difference was examined continuously and dichotomously (>/=5 years). We examined inverse probability of exposure weighted survival curves and calculated time-specific risk differences and risk ratios over 5.5 years of follow-up. We also used a marginal structural Cox model to estimate hazard ratios over the entire study period. RESULTS: Risk of HIV was higher in AGYW with an age-disparate partnership versus not and the risk difference was largest at later time points. At 5.5 years, AGYW with an age-disparate partnership had a 12.6% (95% confidence interval 1.9-23.3) higher risk than AGYW with no age-disparate partnerships. The weighted hazard ratio was 1.91 (95% confidence interval 1.33-2.74), an association that remained after weighting for either transactional or condomless sex, and after examining continuous age-differences. CONCLUSION: Age-disparate partnerships increased risk of HIV infection, even after accounting for transactional sex and condomless sex. The relationship between age-disparate partnerships and HIV infection may be explained by increased exposure to infection from men in a higher HIV prevalence pool rather than differences in sexual behaviour within these partnerships.