Interatrial block (IAB) is associated with an increased risk of atrial fibrillation (AF). The aim of this retrospective study was to investigate the association of a combination of IAB and the CHADS(2) score, an AF-related risk score for ischemic stroke, With new onset AF in patients in sinus rhythm. A total of 1,571 patients (803 males, 768 females; mean age: 58 16 years) were included in this study. IAB was defined as a P-wave duration > 120 ms in the 12-lead electrocardiogram, and a high CHADS(2) score as >= 2 points. During the mean follow-up period of 4.8 +/- 0.7 years, new onset AF occurred in 122 patients (16.1 per 1,000 patient-years). The incidence of new onset AF was 4.0 per 1,000 patient-years in patients with no IAB and a low CHADS(2) score, and 44.0 per 1,000 patient-years in patients with IAB and a high CHADS(2) score. In multivariate Cox regression analysis, the hazard ratio for IAB and a high CHADS(2) score compared with no IAB and a low CHADS(2) score was 12.18 (95% confidence interval: 6.22-23.87, P < 0.001), after adjustment for age, sex, coronary artery disease, valvular heart disease, smoking, medications, and echocardiographic parameters. In conclusion, IAB and a high CHADS(2) score independently and synergistically predict new onset AF in patients in sinus rhythm, indicating an approximately 12-fold higher risk in patients with both IAB and a high CHADS(2) score. Patients meeting these criteria should have more aggressive early intervention to prevent AF.