Vascular remodeling of distal pulmonary arterioles that promotes abnormal pulmonary vascular reactivity is a central mechanism in the pathogenesis of pulmonary arterial hypertension (PAH). In selected patients, invasive pulmonary vasoreactivity testing performed in the cardiac catheterization laboratory with inhaled nitric oxide, epoprostenol, or adenosine is useful for PAH diagnosis, risk stratification, and assessing patient appropriateness for PAH-specific treatment(s). Limited accessibility to inhaled nitric oxide and a suboptimal test sensitivity profile reported for adenosine has contributed to the selection of epoprostenol for pulmonary vasoreactivity testing in some pulmonary hypertension referral centers. However, standardized procedural protocols for administrating epoprostenol for this purpose are largely unavailable to the practicing clinical community. The current work aims to bridge this gap by providing a stepwise procedure for the safe administration of clinically indicated intravenous epoprostenol during pulmonary vasoreactivity testing.