This paper examined gender differences in Quality of Life (QOL) among people living with HIV/AIDS in South India using the locally validated version of the WHO Quality of Life Instrument for HIV (WHOQOL-HIV 120). Participants (N = 109) were men and women with HIV1 Clade C infection participating in a cohort study. There was no gender difference in CD4 counts or use of antiretroviral therapy. Of the 29 facets of QOL, men reported significantly higher QOL in the following facets-positive feeling, sexual activity, financial resources and transport, while women reported significantly higher QOL on the forgiveness and blame facet. Of the six domains of QOL, men reported better quality of life in the environmental domain while women had higher scores on the spirituality/religion and personal beliefs domain. Understanding these gender differences may provide potentially useful information for tailoring interventions to enhance QOL among people infected with HIV/AIDS.