Background: Chronic obstructive pulmonary disease (COPD) is the fourth most frequent disease globally, and its worldwide prevalence is projected to increase in the following decades. Health-related quality of life (HRQOL) of COPD patients depends on multiple factors. Objective: The aim of this study was to identify the most important risk factors affecting HRQOL of COPD patients and to measure how specific clinical parameters can predict HRQOL. Methods: A questionnaire-based cross-sectional study combined with clinical data was conducted among patients diagnosed with COPD (n 5 321, 52.6% females, mean age 66.4 } 9.5) at the National Koranyi Institute for Pulmonology, Budapest in 2019.2020. The inclusion criteria were age .40 years and existing COPD. Multivariate linear regression analyses were conducted on three components of the COPD-specific Saint Georgefs Respiratory Questionnaire (SGRQ-C) and on the physical (PCS) and mental component scales (MCS) of the 36-Item Short Form Health Survey (SF-36). Multiple linear regression analysis was performed to evaluate the effects of patient and disease characteristics on COPD Assessment Test (CAT) scores. Results: We found that frequent exacerbations, multiple comorbidities and tobacco smoking were associated with worse HRQOL. Engaging in more frequent physical activity and better 6-minute walking distance results were associated with better HRQOL. Conclusions: Our results indicate that the complex therapy of COPD should focus not only on improving lung functions and preventing exacerbation, but also on treating comorbidities, encouraging increased physical activity, and supporting smoking cessation to assure better HRQOL for patients.  Kulcsszavak: chronic obstructive pulmonary disease, quality of life, SF-36, SGRQ-C, CAT