OBJECTIVES: A mixed methods study exploring gender differences in patient profiles and experiences of ART services, along the access dimensions of availability, affordability and acceptability, in two rural and two urban areas of South Africa. METHODS: Structured exit interviews (n = 1266) combined with in-depth interviews (n = 20) of women and men enrolled in ART care. RESULTS: Men attending ART services were more likely to be employed (29%vs. 20%, P = 0.001) and were twice as likely to be married/co-habiting as women (42%vs. 22%P = 0.001). Men had known their HIV status for a shorter time (mean 32 vs. 36 months, P = 0.021) and were also less likely to disclose their status to non-family members (17%vs. 26%, P = 0.001). From both forms of data collection, a key finding was the role of female partners in providing social support and facilitating use of services by men. The converse was true for women who relied more on extended families and friends than on partners for support. Young, unmarried and unemployed men faced the greatest social isolation and difficulty. There were no major gender differences in the health system (supply side) dimensions of access. CONCLUSIONS: Gender differences in experiences of HIV services relate more to social than health system factors. However, the health system could be more responsive by designing services in ways that enable earlier and easier use by men.