Health-related quality of life (HRQoL) is an important outcome to assess among persons living with HIV/AIDS, but few studies have been conducted in sub-Saharan Africa. We examined HRQoL among 1180 ART-initiating adults from six clinics in Ethiopia in 2012-2013, and compared the correlates of two subscale scores between women and men. Women scored significantly higher than men on both overall function (8.4 points higher) and life satisfaction (6.3 points higher). In multivariable models, psychological distress, low CD4+ count, unemployment, and food insecurity were associated with lower quality of life scores among women and men. Men whose last sexual encounter occurred 3 months to 1 year from the interview date had lower overall function and life satisfaction scores. Men between the ages of 30-39 had lower overall function scores. Protestant women and women in the low-middle social support category had lower life satisfaction scores. Assessment of HRQoL over time will help inform HIV care and treatment practices to ensure favorable patient outcomes.