Background: HIVAIDS clients now have prolonged survival due to advances in antiretroviral management. Traditional health indicators like mortality and morbidity, used in measuring impact of disease burden and outcome of intervention are quantitative in approach. This study compared HIV positive support and non-support group memberships for predictors of quality of life (QoL) in a tertiary hospital in a South-eastern State in Nigeria. Methods: This was an institution based comparative study of 482 HIV positive clients selected using a two -stage sampling. Data collection was by interview using WHOQOLHIV-Bref and semi-structured questionnaire, while analysis was with statistical package for social sciences version 22.0 and considered p values < 0.05 as statistically significant. Results: Predictors of QoL varied with domain thus: age 30 -39 years (OR=2.678), males (OR= 2.175); the employed (OR=1.864) family support (OR=1.671), the asymptomatic (OR=3.986), good adherence (OR=3.114).in physical domain; Support group membership (OR=1.851), age 30 =39 years (OR=2.445), males (OR=3.639), family support (OR=2.555), tested positive >14 years (OR=4.945), asymptomatic (OR=1.938), good adherence (OR=2.884), in psychological domain. Support group membership (OR=3.303) the asymptomatic (OR=2.907), at most primary education (OR=0.454) in level of independence domain; the married (OR=1.833), family support (OR=2.202) in social relationships domain; the employed (OR=2.332), family support (OR =1.727), the asymptomatic (OR=3.065), good adherence (OR=1.926) in environment domain; age 30-49 years, married (OR=1.605), family support (OR=2.331), the asymptomatic (OR=2.012), good adherence (OR=2.335) in spirituality domain. Conclusions: Some sociodemographic, individual and clinical factors are predictors of QoL, depending on domain assessed. These findings should be put in perspective in designing interventions tailored to the unique needs of these clients.