Background Irreversible, severe pulmonary hypertension (PH) can produce right heart failure and early mortality after cardiac transplantation. We hypothesized that dipyridamole, an inhibitor of Type 5 phosphodiesterase, would augment the ability of inhaled nitric oxide (NO) to identify reversibility of PH. Methods In 9 patients with congestive heart failure (CHF) and severe PH who were breathing 100% oxygen during right heart catheterization, we administered inhaled NO (80 ppm) alone and in combination with intravenous dipyridamole (0.2-mg/kg bolus, with an infusion of 0.0375 mg/kg/min). Results Compared with breathing oxygen alone, NO inhalation decreased pulmonary artery pressure and pulmonary vascular resistance (PVR) (by 10 ± 4% and 26 ± 12% [mean ± SEM], respectively; both p < 0.05). The combination of NO and dipyridamole reduced PVR (43 ± 7%; p < 0.05) to a greater extent than did administration of NO alone, and increased the duration of pulmonary vasodilation produced by NO inhalation. Combined administration of inhaled NO and intravenous dipyridamole increased cardiac index (by 23 ± 10%) and reduced SVR (by 19 ± 6%, both p < 0.05) without changing systemic arterial pressure. NO inhalation reduced PVR to <200 dyne ·s/cm 5 in 3 of 7 patients who had a PVR of >200 dyne · s/cm 5 when breathing oxygen alone, whereas the combination of NO and dipyridamole decreased PVR to <200 dyne · s/cm 5 in 2 additional patients. Conclusions Intravenous dipyridamole augments and prolongs the pulmonary vasodilator effects of inhaled NO in CHF patients with severe PH and, when administered in combination with NO inhalation, can identify PH reversibility in potential cardiac transplant recipients in whom a pulmonary vasodilator response to inhalation of NO alone is not observed.