Introduction and Hypothesis: Data on the efficacy and safety of factor Xa (FXa) inhibitors in chronic thromboembolic pulmonary disease (CTEPD) patients, especially in chronic thromboembolic pulmonary hypertension (CTEPH) patients, remain limited. Here, we aimed to evaluate the effect of FXa inhibitors by measuring anti-factor Xa activity (AXA) in both patients with CTEPD without pulmonary hypertension (PH) and CTEPH. Methods: Twenty-five CTEPD patients without PH and 52 CTEPH patients, treated with either of the FXa inhibitors were enrolled. AXA was measured by using HemosIL heparin calibrator. Blood samples were collected two times at the same day: immediately before the drug administration (trough) and 2-3 h after drug administration (peak). Results: In all 77 patients, median age was 66 (Interquartile range [IQR] 51–73) years, and 43% were male. In addition, 47% of the patients received rivaroxaban of 15 mg/day, 27% received apixaban of 10 mg/day, 14% received edoxaban of 60mg/day, and 12% received edoxaban of 30 mg/day. The median peak AXA of all 77 patients was 1.92 IU/mL and was comparable between CTEPD without PH and CTEPH patients. Significant difference of trough and peak AXA was shown among four different prescribed drugs (P < .001 and P = .006, respectively). During the observational period of median 519 (IQR 364–1118) days, major and clinically relevant non-major bleeding occurred in six patients. ROC analysis to predict bleeding events revealed that the sensitivity and specificity of the cutoff point of a peak AXA of 2.1 IU/mL were 67% and 66%, respectively (AUC 0.66). The cumulative rate of major and clinically relevant non-major bleeding tended to be higher in patients with peak AXA ≥ 2.1 IU/mL than in patients with values below this point (p = .092, Figure). Conclusion: Measuring AXA could be a useful method to evaluate the effect of FXa inhibitors in CTEPD with or without PH patients.