Background Hepatitis C virus (HCV) infection not only links closely to systemic inflammation but also has numerous extrahepatic manifestations. Chronic inflammation also increases the risk of new-onset atrial fibrillation (AF). However, little is known regarding the clinical association between HCV infection and new-onset AF. Methods and Results We conducted a population-based cohort study using Taiwan's National Health Insurance Research Database during 1997 to 2013. A total of 11 771 HCV-infected patients were included in this study, and each of them was matched in a ratio of 1:4. Because of higher mortality among HCV cohorts, we used both Cox proportional hazard regression and competing risk regression models to compute the hazard ratios accompanying 95% CIs after adjustment for relevant confounder. The results demonstrated that the patients with chronic HCV infection had significantly higher incidence rate (332.0 versus 265.8 in 100 000 person-years, P<0.0001) of new-onset AF compared with the non-HCV population. The adjusted hazard ratio of HCV for new-onset AF was 1.32 (95% CI, 1.20-1.44; P<0.0001) and 1.20 (95% CI, 1.10-1.31; P=0.0001) while calculated with Cox proportional hazard regression model and competing risk model, respectively. Intriguingly, we observed that the patients with HCV treated with antiviral agents had significantly lower incidental AF than those without anti-HCV treatment (1.2% versus 6.0%; P<0.0001). Conclusions Chronic HCV infection was associated with an increased risk of incidental AF probably through sharing common pathology of chronic inflammation. Furthermore, a well-designed study is needed to clarify whether anti-HCV therapy can provide protection against the occurrence of AF.