Purpose To investigate the prevalence of and risk factors associated with dry eye syndrome (DES) in South Korea. Design Cross-sectional study. Methods In 2010 and 2011, 11,666 subjects, ranging in age from 19 to 95, were randomly selected as nationally representative participants in the Korea National Health and Nutrition Examination Survey (KNHANES). Subjects were divided into 2 groups: 1 with clinically diagnosed DES and 1 with symptoms of dry eye. We determined the prevalence of and risk factors for dry eyes in a Korean population. Health-related quality of life (HRQoL), measured by the EuroQoL-5 dimension (EQ-5D), was evaluated in patients with dry eyes. Results The mean age was 49.9 years. The overall prevalence of diagnosed DES was 8.0% (95% confidence interval [CI], 7.3% to 8.7%), and of dry eye symptoms the prevalence was 14.4% (95% CI, 13.1 to 15.7). Age (adjusted odds ratio [aOR] = 1.8, 1.6), female (aOR = 2.8, 1.9); history of eye surgery (aOR = 2.6, 2.2); stress (aOR = 1.7, 1.6); thyroid disease (aOR = 1.7, 1.5); and high education level (aOR = 1.6, 1.5) were common risk factors in the groups. Subjects who had undergone ptosis, cataract or refractive surgery were more likely to have dry eye than subjects with no history of eye surgery. Means of pain and anxiety dimensions in the EQ-5D and the Euro Quality of Life Visual Analog Scale (EQ-VAS) were significantly higher in the group with diagnosed DES than in the normal group. Conclusions The risk factors were mostly similar in both groups. It is thought there are more patients with DES who have not been diagnosed by doctors. Doctors should identify whether a patient has any risk factors for dry eye. Patients need to be educated about the modifiable factors of DES.