Background: It has been demonstrated that sildenafil is effective in patients with pulmonary arterial hypertension (PAH). However, the impact of sildenafil on PAH in adults with congenital heart disease (CHD) has been less investigated. Objective: In this prospective, open-label, uncontrolled and multicenter study, 60 patients with PAH related to CHD received oral sildenafil (75 mg/day) for 12 weeks. The enrolled patients underwent six-minute walk test (SMWT) and cardiac catheterization at the beginning and the end of the 12 weeks. The primary end point was the changes in exercise capacity assessed by SMWT; the secondary end point included assessment of functional class, evaluation of cardiopulmonary hemodynamics, and clinical worsening (defined as death, transplantation, and rehospitalization for PAH). Drug safety and tolerability were also examined. Results: Oral sidenafil significantly increased SMWT distances (422.94 ± 76.95 m vs. 371.99 ± 78.73 m, P < 0.0001). There was also remarkable improvement in Borg dyspnea score (2.1 ± 1.32 vs. 2.57 ± 1.42, P= 0.0307). Moreover, significant improvements in World Healthy Organization (WHO) functional class and cardiopulmonary hemodynamics were also discovered (mean pulmonary artery pressure, P= 0.0002; cardiac index, P < 0.0001; pulmonary vascular resistance, P < 0.0001). Side effects in this study were mild and consistent with reported studies. None of the enrolled patients experienced significant clinical worsening. Conclusions: This study confirmed and extended previous studies. It suggested that oral sildenafil was safe and effective for the treatment of adult patients with CHD-related PAH. © 2010 Blackwell Publishing Ltd.