Purpose: The purpose of this study was to investigate the factors that influence health-related quality of life in patients with atrial fibrillation. Methods: The subjects were 150 outpatients with atrial fibrillation who visited the cardiology clinic of a university hospital in U city. The instruments used for this study were Mhel Uncertainty in Illness Scale (MUIS), Center for Epidemiologic Studies-Depression Scale (CES-D), State Trait Anxiety Inventory (STAI), and the Short-Form-36 Health Survey (SF-36) Korean version II. The date were analyzed by ANOVA, Pearson-correlation coefficient, and hierachial multiple regression using SPSS/WIN 18.0. Results: The mean score of physical health-related quality of life (PCS) was $38.92{pm}6.22$ and mental health-related quality of life (MCS) was $41.49{pm}5.71$. Physical and Mental health-related quality of life had the significant correlations with uncertainty, anxiety and depression. In multiple regression analysis, physical health-related quality of life was significantly influenced by duration of disease, NYHA class, uncertainty. Mental health-related quality of life was significantly influenced by family income, NYHA class, anxiety and depression. Conclusion: These results suggest that these influencing factors should be consider in developing the nursing interventions to improve the healthrelated quality of life in patients with atrial fibrillation.