Although the impact of vision-related quality of life (VRQoL) is assessed optimally using binocular visual acuity (VA), uniocular VA remains the preferred measurement method in clinic-based and epidemiologic studies. We compared the impact of distance presenting binocular VA and uniocular VA in the better-seeing (better-eye VA) and worse-seeing (worse-eye VA) eye on VRQoL. The Singapore Chinese Eye Study 2 (2015-2017), a population-based, cross-sectional study. One thousand eight hundred twenty-two individuals (mean age, 66.2 years [standard deviation, 8.9 years]; 51.1% women) were included. Presenting uniocular VA and binocular VA were assessed using a logarithm of the minimum angle of resolution number chart at a distance of 4 m under standard lighting by trained and certified study optometrists. Multiple linear regression models were constructed to determine the independent associations between binocular VA, better-eye VA, and worse-eye VA and the outcome (VRQoL), adjusted for potential confounders, including age, gender, socioeconomic status, and presence of comorbidities. In addition, a cluster sandwich estimator was used to determine if any differences in β estimates between the associations were statistically significant. Vision-related quality of life was measured using Rasch-transformed scores from the emotional, mobility, and reading domains of the Impact of Visual Impairment (IVI) questionnaire. Although every 2-line increase (worsening) in binocular VA and uniocular VA was associated independently with decrements in emotional, mobility, and reading IVI scores (P < 0.05 for all), the reductions in all VRQoL domains were substantially lower (P < 0.1) when using either the better-eye VA (compared with binocular VA β-estimates, -27.8%, -19.4%, and -24.2% difference in emotional, mobility, and reading IVI scores, respectively) or worse-eye VA (compared with binocular VA β estimates, -38.9%, -58.1%, and -57.5% reduction in emotional, mobility, and reading IVI scores, respectively) to quantify vision loss. Uniocular VA seems to underestimate the impact of vision loss on VRQoL indices compared with binocular VA. Our data suggest that researchers, clinicians, and policy planners should consider using binocular instead of uniocular measures of VA in patient-reported outcome evaluation of vision loss because it may better reflect its impact on VRQoL.