IntroductionSouth Africa is a country known for its high levels of HIV infection and sexual violence. Although the interface between gender-based violence, HIV and mental health has been described, there are substantial gaps in knowledge of the medium-term and long-term health impact. The 2010 Global Burden of Disease study excluded many health outcomes associated with rape and other forms of gender-based violence because systematic reviews revealed huge gaps in data and poor evidence of health effects. This study aims to describe the incidence and attributable burden of physical and mental health problems (including HIV acquisition) in adult women over a 2-year postrape period, through comparison with a cohort of women who have not been raped. The study will substantially advance our understanding of the impact of rape and will generate robust data to assist in the development of postrape health services and the delivery of evidence-based care.Methods and analysisThis longitudinal study seeks to recruit 1008 rape-exposed and 1008 rape non-exposed women. Women were recruited from health services, and assessments were carried out at baseline, 3, 6, 9, 12, 18 and 24 months. Outcome measures include exposure to risk factors; mental health status; cardio-metabolic risks; and biomarkers for HIV, sexually transmitted infections, pregnancy and stress. The primary analysis will be to compare HIV incidence in the two groups using log-rank tests. Appropriate models to predict health outcomes over time will also be applied.Ethics and disseminationThe South African Medical Research Council’s Ethics Committee approved the study. As rape is a key element of the study, the safety and protection of participants guides the research process. We will adopt a research uptake strategy to ensure dissemination to policy makers, service providers and advocacy groups. Peer-reviewed journal articles will be published.