PURPOSE: To assess the determinants of image quality of Heidelberg Retina Tomography II (HRT II) and its association with optic disc parameters in a population-based setting. DESIGN: Population-based, cross-sectional study involving 3280 (78.7% response) Asian Malays aged 40 to 80 years. METHODS: Three thousand fifty-six participants completed the HRT II test. Image quality was assessed using the mean pixel height standard deviation generated by the HRT II, with lower mean pixel height standard deviation indicating higher quality. Participants underwent an interviewer-administered questionnaire and a standardized ophthalmic examination, including visual acuity, applanation tonometry, gonioscopy, refraction, automated perimetry, and lens and fundus photography. RESULTS: The mean (standard deviation) and median of mean pixel height standard deviation in the study population were 34 (34) and 23 μm respectively. In multivariate regression models, older age and the presence of visual impairment, blindness, high myopia, and cataract were significantly associated with greater mean pixel height standard deviation (P<.05 for all). People with a higher mean pixel height standard deviation were more likely to have smaller rim area and greater cup depth. CONCLUSION: People who are older or have high myopia, visual impairment, blindness, or cataract are more likely to have poor HRT II image quality. Poorer image quality is in turn associated with smaller optic rim area and greater cup depth. These data provide useful information when the HRT instrument is used for diagnosing glaucoma in the general population.