The aim of the article is to compare the clinical and behavioural characteristics of HIV-infected South Indian patients in concordant and discordant heterosexual relationships. A cross-sectional analysis of married couples in concordant and discordant relationships was carried out. Demographic and clinical characteristics, sexual behaviours, CD4 cell count and plasma HIV-1 RNA loads were assessed. A total of 839 concordant patients and 996 discordant patients were included in this analysis. Significantly more men were in discordant than concordant relationships (97% versus 59%; P = 0.002). More discordant patients had never initiated highly active antiretroviral treatment (HAART) than concordant patients (14.1% versus 8.5%; P = 0.004). Concordant patients had significantly higher CD4 cell counts than discordant patients at the time of enrolling to care (205 versus 139 cells/microL; P = 0.001). Discordant patients had significantly higher plasma viral loads than concordant patients (100,000 copies/mL versus 89,154 copies/mL; P = 0.002). Discordant patients were more likely to use condoms with their spouses than concordant patients (49% versus 28.8%; P = 0.01). In conclusion, couples-based interventions and the provision of HAART could substantially decrease behavioural and clinical correlates of HIV transmission among discordant South Indian married couples. The spouses of HIV-infected index patients are at increased risk for HIV infection, and further preventive measures are needed.