IMPORTANCE Visual impairment (VI) causes a considerable public health burden and substantial deterioration in health-related quality of life (HRQoL). However, the relative effect of VI on HRQoL compared with other chronic health conditions is unknown as is the additive effect of VI with other conditions. OBJECTIVE To investigate whether the impact of chronic health conditions on HRQoL varies according to VI presence. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study involving 29 639 participants aged 19 years and older and using a multistage, probability-cluster survey, which can produce nationally representative estimates. We analyzed data from the 2008-2012 Korean National Health and Nutrition Examination Survey, which included results for vision assessment and HRQoL, measured using the European Quality of Life-5 Dimensions Questionnaire (EQ-5D). All analyses were conducted in October and November 2014. Visual impairment was defined as the presenting distance best-corrected visual acuity of less than decimal 0.32 (approximate Snellen equivalent 20/63). Linear regression models accounting for sample weights were used to examine interactions between VI and each of 14 chronic health conditions on the EQ-5D index score, adjusted for demographic and socioeconomic covariates. MAIN OUTCOMES AND MEASURES The EQ-5D index score for participants with VI or 14 chronic health conditions, as well as the effect of the interactions between VI and each condition on the EQ-5D index score. RESULTS The EQ-5D index score with VI was substantially lower than without VI (mean difference, â0.158; 95% CI, â0.186 to â0.130; P < .001). In most conditions, the comorbidity with VI resulted in lower EQ-5D index scores; furthermore, participants with stroke, osteoarthritis or rheumatic arthritis, hepatitis B or C, and depression showed lower EQ-5D index scores than expected when they were comorbid with VI, indicating an interaction between VI and each condition. The estimated β coefficients for interaction terms were â0.256 (95% CI, â0.480 to â0.032) for stroke, â0.124 (95% CI, â0.223 to â0.026) for osteoarthritis or rheumatic arthritis, â0.183 (95% CI, â0.327 to â0.038) for hepatitis B or C, and â0.130 (95% CI, â0.229 to â0.032) for depression. CONCLUSIONS AND RELEVANCE These results suggest that VI has a substantial effect on HRQoL, even in the presence of concurrent chronic health conditions, and the combined effect of VI and stroke, osteoarthritis/rheumatic arthritis, hepatitis, or depression on HRQoL was greater. However, because this study group was a representative sampling of South Koreans, generalization to other races/ethnicities and countries should be approached with caution.