We investigated whether growth diferentiation factor-15 (GDF-15), also known as macrophage inhibitory cytokine-1 (MIC1), levels are associated with a prothrombotic state in atrial fbrillation (AF) as compared to N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (cTnI-hs). In 103 patients with AF assessed of anticoagulation (age: 71.0 [65.0–76.0] years; CHA2DS2-VASc score: 4.6±1.7), we measured endogenous thrombin potential (ETP), plasma fbrin clot permeability (Ks, a measure of clot density) and clot lysis time (CLT) and other hemostatic parameters, along with GDF-15, NT-proBNP, and cTnI-hs. GDF-15 positively correlated with ETP and CLT (r=0.25, P=0.01 and R=0.56, P<0.0001, respectively) but not with Ks, von Willebrand factor, thrombin-activatable fbrinolysis inhibitor, plasminogen, antiplasmin or tissue-type plasminogen activator antigen. NT-proBNP showed a stronger association with ETP (r=0.60, P<0.0001) and a similar correlation with CLT (R=0.53, P<0.0001), while cTnI-hs correlated solely with CLT (R=0.25, P=0.01). After adjustment for clinical and laboratory parameters, GDF-15 was a better independent predictor of CLT (unstandardized coefcient B 0.009; 95% confdence interval [CI] 0.006–0.012) than NT-proBNP (B 0.007; 95% CI 0.004–0.010, R (2)=0.51; P<0.0001); while among the three biomarkers, only NT-proBNP was an independent predictor of ETP. Elevated GDF-15 and NT-proBNP independently predict impaired fbrin clot lysability, while NT-proBNP is a key predictor of heightened thrombin formation in AF. Our fndings suggest that a predictive value of NT-proBNP and GDF-15 in AF could be in part attributed to their association with prothrombotic blood alterations.