Exercise hemodynamics are recommended for early detection of pulmonary arterial hypertension (PAH) and have been suggested to be predictive of future development of PAH in high-risk populations such as bone morphogenetic protein receptor type 2 (BMPR2) mutation carriers. However, the optimal exercise hemodynamic screening parameter remains to be determined. Recent data suggest that pulmonary vascular distensibility coefficient (α) may serve as a useful parameter for early detection of PAH. What is the value of exercise hemodynamics, including α, for predicting the occurrence of PAH during long-term follow-up in BMPR2 mutation carriers? 52 asymptomatic BMPR2 mutation carriers who underwent symptom-limited exercise hemodynamic assessment were followed for a median of 10 years. The impact of hemodynamics at rest and exercise, presence of exercise PH and α on occurrence of PAH during long-term follow-up was assessed. During long-term follow-up 5 patients developed PAH. Patients who developed PAH had a significantly lower α (0.8±0.4%/mmHg) than patients without PAH (1.8±0.8%/mmHg, p=0.008). α was the only hemodynamic parameter that predicted the occurrence of PAH during long-term follow-up at regression analysis. At receiver operating characteristic analysis α ≤1.5%/mmHg predicted PAH occurrence with a specificity of 75% and sensitivity of 100%. α is markedly reduced prior to development of PAH in BMPR2 mutation carriers and may serve as a useful parameter in the setting of early disease detection. Given the low event rate, caution is warranted in interpreting these results, highlighting the need for validation studies.