HIV continues to cause the largest number of disability-adjusted life years of any disease in HIV hyperendemic countries (i.e., countries with an adult HIV prevalence >15%). We compare the benefits and costs of two proven biological interventions to reduce the health losses due to the HIV epidemic in hyperendemic countries from 2015 through 2030: 1) increasing ART coverage to 90% among HIV-infected adults with a CD4-cell count <350 cells/microliter, before expanding the HIV treatment scale-up to people with higher CD4-cell counts; and 2) increasing male medical circumcision coverage to at least 90% among HIV-uninfected adult men. We developed a mathematical model to determine the benefits and costs of increasing the coverage of both ART under different CD4-cell count thresholds and of circumcision in HIV-hyperendemic countries. The results show that scaling up ART and circumcision are both cost-beneficial. However, the benefit-to-cost ratio (BCR) for circumcision is significantly higher than for ART: 7.4 vs. 3.0 (at US$1,000 per life year and a 5% discount rate) and 56.4 vs. 16.3 (at US$5,000 per life year and a 3% discount rate). The additional cost of scaling up circumcision is approximately $US500 million while the additional cost of increasing ART coverage lies between $US17 and $US19 billion. We conclude that increasing the coverage of ART among HIV-infected adults with a CD4-cell count <350 cells/microliter and, in particular, scaling up male medical circumcision among HIV-negative men are both highly cost-beneficial interventions to reduce the health burdens resulting from the HIV epidemic in hyperendemic countries over the next 15 years.