Transactional sex (TS) has been shown to contribute to the HIV epidemic in sub-Saharan Africa. Previous research has yet to identify psychosocial factors that make young women vulnerable to engaging in TS. This analysis examined the association between self-esteem and TS among young women in rural South Africa. A post hoc analysis of post-intervention survey data from HPTN 068 was conducted. Log-binomial regression was used to compute a prevalence ratio measure of association. Among 1942 young women, the prevalence of TS among those with lower self-esteem was 4.7 times the prevalence of TS among those with higher self-esteem (p < 0.001). Findings provide support for the association between lower self-esteem and TS in this context and may inform intervention development.