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. 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. 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). 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. 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).