Quality of life is not well studied in atrial fibrillation (AF), the most prevalent rhythm disturbance with significant impact on morbidity and mortality. We report the development of a brief disease-specific QOL instrument for use in clinical trials, surveillance studies, and clinical practice. METHODS: 51 items, based on literature, patient focus groups, and a cardiology expert panel were administered via telephone interview to 73 chronic AF and 23 congestive heart failure (CHF) and 25 angina control patients. RESULTS: Item reduction techniques produced the 20-item AFIS comprising 4 symptom scales (dyspnea, fatigue, palpitations syncope; 11 items) and 3 QOL scores measuring functional, social and emotional impact (9 items). Internal consistencies were acceptable for all symptom scales (Cronbach (’s 0.73 to 0.77) and the QOL scales (Cronbach (’s 0.74 to 0.92). AFIS Total Symptom Impact (SI) score explained 50% of the variation in each QOL impact score (R2 = 0.49 (functional), 0.44 (emotional), 0.55 (social)) and 75% (R2 = 0.74) of the total QOL impact (QI) score. We identified two symptom impact (SI) threshold scores: moderate AF impact (SI = 40; sensitivity 0.86, 1-specificity 0.92) and major AF impact (SI = 60; sensitivity 0.96, 1-specificity 0.98). Mild symptomatic CAF patients (SI < 40) reported little QOL interference. Moderate symptomatic and major symptomatic CAF patients had QI scores 200% and 665% worse than the mild CAF patients. SI scores accounted for 50% (R2 = 0.50) and nearly 25% (R2 = 0.22) of total QI variation in CHF and angina patients, respectively. CONCLUSION: Mild AF symptoms are well tolerated. However moderate symptom impact (over 50% of patients) doubles the interference with QOL while major impact (33% of patients) approached a seven-fold worsening of QOL. The AFIS appears to be a useful tool for predicting worsening QOL among AF patients and for informing treatment decisions.