Background: It is important to identify patients with co-morbid acute coronary syndrome (ACS) and atrial fibrillation (AF) at high risk and adopt proper management strategies to improve their prognosis.Hypothesis: The addition of N-terminal pro-B-type natriuretic peptide (NT-proBNP) could improve predictive value for long-term cardiovascular events beyond the CHA 2 DS 2 -VASc score in patients with co-morbid ACS and AF.Methods: A total of 1223 patients with baseline NT-proBNP between January 2016 and December 2019 were included in the study. The primary endpoint was all-cause death at 12 months. The secondary outcomes included 12-month cardiac death and major adverse cardiovascular and cerebrovascular event (MACCE), defined as a composite of all-cause death, myocardial infarction, or stroke.Results: A higher serum of NT-proBNP levels was strongly associated with increased risks of all-cause death (adjusted hazard ratio [HR]: 1.05, 95% confidence interval [CI], 1.03-1.07), cardiac death (adjusted HR: 1.05, 95% CI, 1.03-1.07), and MACCE (adjusted HR: 1.04, 95% CI, 1.02-1.06). The prognostic accuracy of the CHA 2 DS 2 -VASc score was improved when combined with NT-proBNP to yield a 9%, 11%, and 7% increment for the discrimination of long-term risk for all-cause mortality (area under curve [AUC]: from 0.64 to 0.73), cardiac death (AUC: from 0.65 to 0.76), and MACCE (AUC: from 0.62 to 0.69), respectively.Conclusions: In patients with ACS and AF, NT-proBNP is a potential biomarker to enhance risk discrimination for all-cause death, cardiac death, and MACCE in combination with the CHA 2 DS 2 -VASc score.