BACKGROUND: Excessive ventilation (V̇E) and abnormal gas exchange during exercise are features ofchronic thromboembolic pulmonary hypertension (CTEPH). In selected CTEPH patients, balloon pulmonaryangioplasty (BPA) improves symptoms and exercise capacity. How BPA affects exercisehyperventilation and gas exchange is poorly understood.METHODS: In this longitudinal observational study, symptom-limited cardiopulmonary exercise testsand carbon monoxide lung diffusion (DLCO) were performed before and after BPA (interval, mean(SD): 3.1 (2.4) months) in 36 CTEPH patients without significant cardiac and/or pulmonarycomorbidities.RESULTS: Peak work rate improved by 20% after BPA whilst V ̇ E at peak did not change despiteimproved ventilatory efficiency (lower V ̇ E with respect to CO2 output [V̇CO2]). At the highestidentical work rate pre- and post-BPA (75 (30) watts), V ̇E and alveolar-arterial oxygen gradient(P(Ai-a)O2) decreased by 17% and 19% after BPA, respectively. The physiological dead spacefraction of tidal volume (VD/VT), calculated from measurements of arterial and mixed expired CO2, decreased by 20%. In the meantime, DLCO did not change. The best correlates of P(Ai-a)O2 measured at peak exercise were physiological VD/VT before BPA and DLCO after BPA.CONCLUSIONS: Ventilatory efficiency, physiological VD/VT, and pulmonary gas exchange improvedafter BPA. The fact that DLCO did not change suggests that the pulmonary capillary blood volume andprobably the true alveolar dead space were unaffected by BPA. The correlation between DLCO measuredbefore BPA and P(Ai-a)O2 measured after BPA suggests that DLCO may provide an easilyaccessible marker to predict the response to BPA in terms of pulmonary gas exchange.