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The HPTN 052 study demonstrated a 96% reduction in HIV transmission in discordant couples using antiretroviral therapy (ART).To predict the epidemic impact of treating HIV-discordant couples to prevent transmission.Mathematical modeling to predict incidence reduction and the number of infections prevented.Demographic and epidemiological data from Ghana, Lesotho, Malawi and Rwanda were used to parameterize the model. ART was assumed to be 96% effective in preventing transmission.Our results show there would be a fairly large reduction in incidence and a substantial number of infections prevented in Malawi. However, in Ghana a large number of infections would be prevented, but only a small reduction in incidence. Notably, the predicted number of infections prevented would be similar (and low) in Lesotho and Rwanda, but incidence reduction would be substantially greater in Lesotho than Rwanda. The higher the proportion of the population in stable partnerships (whether concordant or discordant), the greater the effect of a discordant couple's intervention on HIV epidemics.The effectiveness of a discordant couples intervention in reducing incidence will vary among countries due to differences in HIV prevalence and the percentage of couples that are discordant (i.e. degree of discordancy). The number of infections prevented within a country, as a result of an intervention, will depend upon a complex interaction among three factors: population size, HIV prevalence and degree of discordancy. Our model provides a quantitative framework for identifying countries most likely to benefit from treating discordant couples to prevent transmission.