OBJECTIVES: The World Health Organization (WHO) recommends task-shifting HIV care to nurses in low-resource settings with limited numbers of physicians. However, the effect of such task-shifting on the health-related quality of life (HRQL) of people living with HIV (PLHIV) has seldom been evaluated. We aimed to investigate the effect of task-shifting HIV care to nurses on HRQL outcomes in PLHIV initiating antiretroviral therapy (ART) in rural district hospitals in Cameroon. METHODS: Outcomes in PLHIV were longitudinally collected in the 2006-2010 Stratall trial. PLHIV were followed up for 24 months by nurses and/or physicians. Six HRQL dimensions were assessed during face-to-face interviews using the WHO Quality of Life (WHOQOL)-HIV BREF scale: physical health; psychological health; independence level; social relationships; environment; and spirituality/religion/personal beliefs. The degree of task-shifting was estimated using a consultant ratio (i.e. the ratio of nurse-led to physician-led visits). The effect of task-shifting and other potential correlates on HRQL dimensions was explored using a Heckman two-stage approach based on linear mixed models to adjust for the potential bias caused by missing data in the outcomes. RESULTS: Of 1424 visits in 440 PLHIV (70.5% female; median age 36 years; median CD4 count 188 cells/μL at enrolment), 423 (29.7%) were task-shifted to nurses. After multiple adjustment, task-shifting was associated with higher HRQL level for four dimensions: physical health [coefficient 0.7; 95% confidence interval (CI) 0.1-1.2; P = 0.01], psychological health (coefficient 0.5; 95% CI 0.0-1.0; P = 0.05), independence level (coefficient 0.6; 95% CI 0.1-1.1; P = 0.01) and environment (coefficient 0.6; 95% CI 0.1-1.0; P = 0.02). CONCLUSIONS: Task-shifting HIV care to nurses benefits the HRQL of PLHIV. Together with the previously demonstrated comparable clinical effectiveness of physician-based and nurse-based models of HIV care, our results support the WHO recommendation for task-shifting.