Acute pulmonary hypertension is a severe and life-threatening reaction that rarely occurs secondary to protamine administration. Management of systemic hypotension combined with severe pulmonary hypertension causing right ventricular failure is challenging. We describe a case of acute pulmonary hypertension induced by protamine during elective coronary artery bypass surgery refractory to multiple systemic inotropic and vasopressor therapies. After inhaled prostacyclin administration, our patient's pulmonary artery pressures decreased from 70/37 to 45/23 mm Hg within 10 min. The case highlights a role for inhaled nebulized prostacyclin as a selective pulmonary vasodilator with minimal systemic hypotensive effects.