Abstract. BACKGROUND: Despite recent treatment modalities, mortality from persistent pulmonary hypertension (PPHN) remains significant. In instances where infants do not respond to inhaled nitric oxide (iNO), oral sildenafil could hold promise as a selective pulmonary vasodilator. Further studies are still needed to explore its efficacy and safety in newborns with PPHN. OBJECTIVES: To validate the efficacy of oral sildenafil on oxygenation and its short-term safety in newborns with persistent pulmonary hypertension. METHODS: A total of 27 newborns ≥36 weeks gestational age were admitted to NICU with oxygenation index (OI) ≥15 and confirmed diagnosis of PPHN with echocardiography. Oral sildenafil given at a dose of 1-2 mg/kg every 6 hours. We monitored improvement in oxygenation, safety and short-term outcomes. RESULTS: Among 27 newborns, oral sildenafil was efficacious in 21 patients (78%) with reduction of OI from 34.9 ± 9.6 to 13 ± 3.2 (p < 0.001), increase of PaO2 from 42.4 ± 13.5 to 78 ± 11.5 mmHg (<0.001), and reduction of FiO2 from 1.0 ± 0 to 0.3 ± 0.06 (<0.001). OI decreased by 6.3 % from baseline after the first dose of sildenafil and continued to decrease with subsequent doses. In 6 patients (22%) sildenafil did not work; 5/6 patients (18%) transferred to another tertiary NICU and one patient (4%) died of sepsis. None of the patients had significant systemic hypotension. CONCLUSION: Oral sildenafil is a promising pulmonary vasodilator in patients with PPHN, particularly in medical facilities with no available iNO and ECMO. It is well tolerated with no significant short term complications.