OBJECTIVES Health-related quality of life (HRQOL) is a key indicator of health. However, HRQOL data from representative populations in South Asia are lacking. This study aims to describe HRQOL overall, by age, gender and socioeconomic status, and examine the associations between selected chronic conditions and HRQOL in adults from three urban cities in South Asia. METHODS We used data from 16 287 adults aged ≥20 years from the baseline survey of the Centre for Cardiometabolic Risk Reduction in South Asia cohort (2010-2011). HRQOL was measured using the European Quality of Life Five Dimension-Visual Analogue Scale (EQ5D-VAS), which measures health status on a scale of 0 (worst health status) to 100 (best possible health status). RESULTS 16 284 participants completed the EQ5D-VAS. Mean age was 42.4 (±13.3) years and 52.4% were women. 14% of the respondents reported problems in mobility and pain/discomfort domains. Mean VAS score was 74 (95% CI 73.7 to 74.2). Significantly lower health status was found in elderly (64.1), women (71.6), unemployed (68.4), less educated (71.2) and low-income group (73.4). Individuals with chronic conditions reported worse health status than those without (67.4 vs 76.2): prevalence ratio, 1.8 (95% CI 1.61 to 2.04). CONCLUSIONS Our data demonstrate significantly lower HRQOL in key demographic groups and those with chronic conditions, which is consistent with previous studies. These data provide insights on inequalities in population health status, and potentially reveal unmet needs in the community to guide health policies.