Background: Male circumcision has health benefits and cultural significance in South Africa and elsewhere. We sought to understand perceptions about male circumcision among participants enrolled in a preventive human immunodeficiency virus (HIV) vaccine efficacy trial in South Africa.Methods: We conducted a qualitative study with 28 consenting people aged 18–35 years old who self-reported that they were not living with HIV and who were participating in the HIV Vaccine Trials Network (HVTN) 702 vaccine efficacy trial in Soweto. Using a semi-structured guide, we facilitated four focus group discussions (FGDs) stratified by age, gender and sexual orientation. Focus group discussions were audio-recorded, transcribed verbatim, translated into English and thematically analysed.Results: Four main themes emerged: (1) accurate knowledge about what male circumcision is, with some participants stating that it partially reduces acquisition of HIV and sexually transmitted infections; (2) emerging distrust of cultural circumcision because of perceived lack of transparency and adverse events; (3) misperceptions that circumcision boosted masculinity and (4) the influenced of parents, family and female partners in circumcision decision-making.Conclusion: Young South African HIV vaccine trial participants accurately understand the HIV prevention benefits of male circumcision, but uptake decisions are embedded within a context informed by culture, sexuality, masculinity norms and values and the influence of women.Contribution: In this study, we showed that young South Africans participating in HIV vaccine trials instead embed their circumcision uptake decisions within a context informed by culture, sexuality and masculinity norms and values and influence of women.