This purpose of this study was to compare factors influencing health-related quality of life (HRQOL) by obesity among middle-aged women. A nationally representative sample of 1,255 middle-aged women (40-60) from the 6th (2014) Korean National Health and Nutrition Examination Survey was analyzed. HRQOL was measured using the Korean version of the EQ-5D (EuroQol-5 Dimensions). The data were analyzed by descriptive statistics, Chi-square test, t-test, and linear regression with SPSS version 23.0 program. As a result, there were statistically significant differences in age, income, education level, and walking days for a week according to obesity. Activities limitation, age, and experience of depression symptoms were significantly associated with HRQOL among obese middle-aged women. Activities limitation, age, experience of depression symptoms, stress cognition, and discomfort experience for nearly 2 weeks were significantly associated with HRQOL among normal weight middle-aged women. Therefore, these variables should be included in nursing interventions to improve HRQOL of middle-aged women, and differentiated interventions for variables such as stress and physical discomfort, which were significantly different depending on obesity, will be needed.