Abstract: AIM:To evaluate the efficacy and safety of sildenafil in treatment of patients with severe pulmonary arterial hypertension (PAH) secondary to congenital heart disease (CHD). METHODS: Patients with severe PAH secondary to systemic-to-pulmonary shunt CHD were treated with sildenafil for 6 months. The dose of sildenafil was 25 mg three times daily in patients weighing ≥50 kg and 0.5 mg/kg thrice daily in children weighing <50 kg. Six-minute walk distance test, echocardiography, cardiac catheterization, complete blood count, and hepatic as well as renal functions were assessed at baseline and after the 6-month therapy. RESULTS: After the 6-month sildenafil treatment, all the patients had a significant increase in the 6-minute walk distance (P<0.01) and 18 of them had symptomatic improvement. No significant changes were observed in echocardiograhic parameters, including right ventricular end-diastolic diameter, left ventricular end-diastolic diameter and volume, and tricuspid regurgitation peak velocity, except the left ventricular ejection fraction (P<0.05). Right heart catheterization showed significant increase in pulmonary-to-systemic flow (Qp/Qs) ratio (P<0.01) and significant decrease in pulmonary vascular resistance (P<0.05) and pulmonary-to-systemic vascular resistance (Rp/Rs) ratio. Simultaneous decrease in Qp/Qs ratio and increase in Rp/Rs ratio were found in 8 (24.2%) of the 33 patients. Adverse events were observed in seven patients, including headache in two patients, flushing in three patients, nasal congestion in one patient, and abnormal penile erection in one teenage male. Significant decreases of red blood cell count (P<0.01) and hemoglobin (P<0.01) accompanied by a mild increase of creatinine (P<0.05) were observed after the 6-month therapy. CONCLUSION: Six-month sildenafil therapy is well tolerated and the therapy markedly improves the exercise capacity and hemodynamics in most patients with severe PAH secondary to CHD.