The aim of this prospective, randomized and controlled study was to compare the clinical efficacy of intravenous magnesium sulfate (MgSO₄) and oral sildenafil therapies with persistent pulmonary hypertension of the newborn. A total of 34 infants in the MgSO₄ group and 31 infants in the sildenafil group completed the study. The time to reach the adequate clinical response [defined as oxygen index (OI) level of <15, a pulmonary artery pressure of < 20 mmHg) was significantly shorter in the sildenafil group (p = 0.002). Duration of mechanical ventilation was longer and the number of the patients requiring inotropic support was higher in the MgSO₄ group (p = 0.001 and p = 0.002, respectively). Although among two groups the difference in OI > 5 as speculated in our hypothesis could only be found at 36 h of the treatment, sildenafil was more effective than MgSO₄ in the treatment of persistent pulmonary hypertension of the newborns with regard to time to adequate clinical response, duration of mechanical ventilation and support requirement with inotropic agents.