OBJECTIVE: The aim of this study was to assess the role of inflammatory processes in the development of atrial fibrillation (AF) and the prognostic impact of inflammatory markers in predicting long-term risk of AF recurrence after electrical cardioversion (CV). METHODS: High-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) were measured in 56 patients with persistent AF (lasting mean 128 days (range 14-960), mean age 65 years (34-84)), 19 healthy volunteers and 19 patients with permanent AF. Patients with persistent AF underwent CV. Blood samples were taken prior to CV and after 1, 30 and 180 days. RESULTS: The immediate success rate of CV was 88%, while the total recurrence rate after 180 days was 68%. Patients with permanent AF had significantly higher levels of hs-CRP and IL-6 than patients with persistent AF (p = 0.0011, p<0.001). Patients in sinus rhythm (SR) after 180 days had significantly lower baseline hs-CRP (1.25 mg/L (0.5-2.4) versus 2.0 mg/L (0.9-3.3), p<0.001) and IL-6 (1.96 pg/mL (1.35-2.7) versus 2.75 pg/mL (1.55-3.62), p<0.001) than patients with recurrent AF. Baseline IL-6 was the only independent predictor of recurrent AF (p = 0.04) in a multivariate Cox analysis. Patients in the lowest hs-CRP quartile (<0.8 mg/L) had significantly lower AF recurrence rates after 180 days (50% versus 74% in the other three quartiles combined; p = 0.0069). CONCLUSION: Patients with AF had elevated levels of inflammatory markers. Low hs-CRP and IL-6 prior to CV are associated with a lower risk of AF recurrence after CV.