Background and aims: The prognostic role of big endothelin-1 (ET-1) in atrial fibrillation (AF) is unclear. We aimed to assess its predictive value in patients with AF.& para;& para;Methods: A total of 716 AF patients were enrolled and divided into two groups based on the optimal cutoff value of big ET-1 in predicting all-cause mortality. The primary outcomes were all-cause mortality and major adverse events (MAEs). Cox regression analysis and net reclassification improvement (NRI) analysis were performed to assess the predictive value of big ET-1 on outcomes.& para;& para;Results: With the optimal cutoff value of 0.55 pmol/L, 326 patients were classified into the high big ET-1 levels group. Cardiac dysfunction and left atrial dilation were factors related to high big ET-1 levels. During a median follow-up of 3 years, patients with big ET-1 >= 0.55 pmol/L had notably higher risk of all-cause death (44.8% vs. 11.5%, p < 0.001), MAEs (51.8% vs. 17.4%, p < 0.001), cardiovascular death, major bleeding, and tended to have higher thromboembolic risk. After adjusting for confounding factors, high big ET-1 level was an independent predictor of all-cause mortality (hazard ratio (HR) 2.11, 95% confidence interval (CI) 1.46-3.05; p < 0.001), MAEs (HR 2.05, 95% CI 1.50-2.80; p = 0.001), and cardiovascular death (HR 2.44, 95% CI 1.52-3.93; p < 0.001). NRI analysis showed that big ET-1 allowed a significant improvement of 0.32 in the accuracy of predicting the risk of both all-cause mortality and MAEs.& para;& para;Conclusions: Elevated big ET-1 levels is an independent predictor of long-term all-cause mortality, MAEs, and cardiovascular death in patients with AF. (C) 2018 Elsevier B.V. All rights reserved.