OBJECTIVE: This study investigated whether the QTc interval on the electrocardiogram (ECG) is associated with onset of atrial fibrillation (AF). BACKGROUND: Patients with hereditary short and long QT syndromes, representing the very extremes of the QT interval, both seem to have a high prevalence of AF. METHODS: We included 281,277 individuals, corresponding to one third of the population in the greater region of Copenhagen. These individuals had a digital ECG recorded in a general practitioner's core facility from 2001-2010. Data on drug use, comorbidity, and outcomes were collected from Danish registers. RESULTS: After a median follow-up of 5.7 years, 10,766 individuals developed AF, hereof 1,467 (14%) lone AF. Having a QTc interval below 1st percentile (≤372ms) was associated with a multivariable-adjusted hazard ratio (HR) of 1.45 (95% confidence interval [CI] 1.14-1.84, P=0.002) for AF, compared with the reference group (411-419ms). From the reference group and upwards, the risk of AF increased with QTc interval duration in a dose-response manner reaching an HR of 1.44 (95% CI 1.24-1.66, P<0.001) for those having a QTc interval ≥99th percentile (≥464ms). The association with respect to longer QTc intervals was stronger for the outcome lone AF as evidenced by an HR of 2.32 (95% CI 1.52-3.54, P<0.001) for having a QTc interval ≥99th percentile (≥458ms). CONCLUSIONS: In this large ECG study, we found a J-shaped association between QTc interval duration and risk of AF. This association was strongest with respect to the development of lone AF.