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The association between health-related quality of life (HRQoL) and ethnicity has been studied among hemodialysis (HD) patients in several countries with varying results. However, the effect of ethnicity on the HRQoL of HD patients in the Asian context has yet to be evaluated. This study seeks to examine the HRQoL of HD patients in Singapore and to understand the influence of ethnicity on their HRQoL.A census-style survey inclusive of the KDQoL-SF. The AMA was conducted among all HD patients from 22 dialysis centers across Singapore. Multiple linear regression models were used to analyze the influence of ethnicity on each SF-36 scale while adjusting for the influence of socioeconomic status (SES) factors and other determinants of HRQoL.Data from 1,249 HD patients were analyzed. Response rate was 63.3%. Compared with other ethnicities, Chinese were most likely to report lower HRQoL. After adjusting for sex, age, and other possible determinants of HRQoL, the influence of ethnicity on HRQoL persisted, with significant mean differences in role-physical, general health, role-emotional, and physical component summary scales.After adjusting for demographic, SES, and other factors, ethnicity remained an important factor influencing HRQoL of Singaporean HD patients. Further studies are needed to identify modifiable factors that might explain the interethnic differences in HRQoL among HD patients.