BACKGROUND: Numerous studies have identified that physical activity (PA) has positive influences on quality of life. However, there has been little domestic research about the relation of PA to health-related quality of life (HRQoL) among the general population. The purpose of this study was to evaluate the effect of PA on HRQoL in Korean adults aged 40 years or over. METHODS: This cross-sectional study was based on data acquired from the Korean National Health and Nutrition Examination Survey IV. Final study subjects were 10,392 adults aged 40 years or over. According to the severity and frequency of PA, the subjects were divided into three PA groups as follows: high-activity, mid-activity, and low-activity group. We compared the HRQoL estimated by the EuroQoL 5-dimension (EQ-5D), the EQ visual analogue scale (EQ-VAS), and EQ-5D index between three PA groups. RESULTS: The odds ratios for mid-activity group and high activity group compared with low activity group were significantly decreased in the dimension of mobility of EQ-5D (mid-activity group, 0.81 [0.69-0.94]; high activity group, 0.81 [0.67-0.99]). EQ-VAS was decreased as PA level was lowered from high activity group and mid-activity to low activity group. EQ-5D index was the highest in mid-activity group and the lowest in low activity group. CONCLUSION: PA above mid-activity group showed better HRQoL compared than low activity group.