Empirical research on ethical issues in HIV-prevention and gender-based violence research, critical for honing ethical and safety guidelines, is limited. In this paper we describe South African young people's motivations for participating in randomised controlled trial, the prevalence of negative occurrences, participation regrets and associated factors. This trial partly followed, but also deviated from, the WHO safety guidelines for research on violence against women. A total of 1085 women and 985 men provided information two years after the trial start. Most participated for HIV testing and to help their community. Fewer reported motivation by the financial incentive. Minor adverse events included upset from questions on childhood experiences and arguments at home with siblings. Just under 1 in 10 (8.1% women, 9.8% men) regretted participation. Factors were associated with this were keeping some questions secret from their partners, feeling sad about questions on childhood, quarrelling at home and, for women, being motivated by the incentive. Men who had been physically violent to a partner were twice as likely to regret participation. There were no recorded adverse effects from the deviations from the ethical guidelines. Participation regrets mostly stemmed from problems in participants' families preceding the research. There was no evidence that the research had been unsafe.