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Introduction: Acceptance of illness plays a key role, allowing the patient to adapt to the disease and its treatment, and to maintain their health-related quality of life (HRQOL) despite chronic conditions. Aim: The aim of the study was to assess the relationship between severity of arrhythmia symptoms, acceptance of illness and HRQOL in patients with atrial fibrillation. Methods: The study included 99 patients (mean age 64.6) treated for atrial fibrillation. Three standardized instruments were used: the World Health Organization Quality of Life (WHOQoL-BREF) questionnaire, the Arrhythmia-Specific Questionnaire in Tachycardia and Arrhythmia (ASTA) and the Acceptance of Illness Scale (AIS). Results: Patients with high illness acceptance levels obtained better results in all WHOQoL-BREF domains: physical (57.0±8.9 vs. 51.1±12.5 vs. 42.0±6.2; p<0.001), social (62.6±19.8 vs. 52.5±20.0 vs. 45.7±16.0; p=0.019) and environmental (62.9±12.7 vs. 52.7±7.6 vs. 60.7±3.6; p<0.001), and in the ASTA HRQOL scale (10.5±5.4 vs. 16.1±7.6 vs. 20.3±0.5; p<0.001). Multiple-factor analysis showed AIS to be a statistically significant independent determinant of HRQOL in the physical domain of the WHOQoL (β=0.242) and in the overall HRQOL assessment in the ASTA HRQOL scale (β= −0.362). Other statistically significant independent predictors included: the negative impact of female sex on the physical (β= −0.291) and social (β= −0.284) domains of the WHOQOL-BREF, and the positive impact of urban residence on the physical WHOQOL-BREF domain and on symptom intensity in the ASTA symptom scale. Conclusions: Acceptance of illness is an important factor which has been shown to impact on HRQOL in atrial fibrillation. Female sex is a predictor of worse HRQOL, while urban residence improves HRQOL in the physical domain and decreases symptom intensity (ASTA symptom scale). [ABSTRACT FROM AUTHOR]