This first independent systematic review examined evidence for the effectiveness of the stepping stones intervention in HIV prevention. To reduce HIV transmission it addresses gender roles and promotes equitable relationships. Biomedical, behavioural and psychosocial outcomes extracted from six databases and 'grey' literature identified eight reports of seven studies (n = 14,630) from India, Gambia, S. Africa, Ethiopia, Angola, Tanzania, Uganda and Fiji. Infection incidence tested in the only RCT showed no significant reduction in HIV, although HSV-2 decreased. Condom use increased (two countries out of eight). Risk reduction results were mixed for declining alcohol misuse (two studies in three) and multiple partners (one in two). Communicating HIV information to partners, family or community improved (three studies from seven). Gender inequity was reduced in India (one in five), but stigma decreased in four studies. Future investigations of diverse cultures and older adults should select high quality biomedical and quality of life measures.