BACKGROUND: Riociguat and balloon pulmonary angioplasty (BPA) improve hemodynamics in inoperable chronic thromboembolic pulmonary hypertension. Importantly, comparative effects of riociguat and BPA on different components of right ventricular (RV) afterload and function remain not fully elucidated. METHODS: We conducted a post hoc analysis including patients from the RACE trial (Riociguat Versus Balloon Pulmonary Angioplasty in Non-Operable Chronic Thromboembolic Pulmonary Hypertension) with complete data for the primary end point assessment (49 riociguat and 51 BPA). Symptomatic patients with a residual pulmonary vascular resistance >4 WU received add-on riociguat after BPA (n=18) or add-on BPA after riociguat (n=36) and were included in an ancillary 26-week follow-up study with hemodynamic reassessment at week 52. RESULTS: Cardiac output, stroke volume, and RV afterload improved significantly with riociguat and BPA, and the relative changes in RV afterload from baseline to week 26 were more pronounced in the BPA group (all P <0.001). Change in RV afterload was primarily mediated by decreased mean pulmonary arterial pressure in the BPA group, while increased cardiac output was the main driver in the riociguat group. Key parameters of RV function (RV stroke work and right atrial pressure) improved only in the BPA group. The ancillary follow-up study confirmed that relative change in RV afterload from week 26 to week 52 was more pronounced with add-on BPA, and improved RV function was only observed in the add-on BPA group. CONCLUSIONS: Both riociguat and BPA are effective in improving RV afterload in inoperable chronic thromboembolic pulmonary hypertension. However, BPA provided a more substantial impact on RV afterload reduction, and RV function only improved with BPA. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02634203.