OBJECTIVES: 1) To validate an existing disease-specific HRQoL instrument culturally adapted for use in English speaking Hepatitis B patients in Singapore; and 2) to evaluate the HRQoL in a cross section of Hepatitis B patients ranging from asymptomatic carriers to those who have undergone liver transplantation. METHODS: A disease-targeted, multi-item scales HRQoL questionnaire, Hepatitis Quality of Life Questionnaire (HQLQ) which covers Hepatitis specifically was validated in a sample of Hepatitis B patients recruited from National University Hospital (NUH), a tertiary referral hospital in Singapore. The cultural adaptation of the instrument was performed by conducting several focus groups. The questionnaire was then used to assess the HRQoL in a cross section of Hepatitis B patients ranging from asymptomatic carriers to those who have undergone liver transplantation. One-way analysis of variance (ANOVA) was employed to test for the statistical significant difference in all scale scores among different categories of Hepatitis B patients. Internal consistency reliability and construct validity were also evaluated. RESULTS: The culturally adapted questionnaire has been tested for its validity and reliability in 170 patients attended the Unit Digestive Centre in NUH. For the validation study of the culturally adapted instrument, reliability coefficients (Cronbach's alpha) were excellent with the total score of 0.97; and for 17 of 20 scales, alpha > 0.7. In the HRQoL evaluation study for Hepatitis B patients, a comparison of mean scale scores at different stages of the disease showed significantly lower HRQoL in cases of more advanced stages of disease in most domains. CONCLUSION: The questionnaire has good cross-sectional validity, making it a potentially useful outcome measure in the evaluation of Hepatitis B patients in Singapore.