The hemodynamic determination of operability in atrial septal defect (ASD) with severe pulmonary hypertension is problematic. Therefore, we perform an open lung biopsy prior to the corrective surgery in cases with pulmonary vascular resistance greater than 8 units · M2 and/or pulmonary arterial peak pressure greater than 70 mmHg. We present 4 cases showing occlusion of more than 70% of the small pulmonary arteries and arterioles by musculoelastosis, thromboembolism and mixed-type (musculoelastosis and plexogenic arteriopathy) which was considered borderline in terms of operability. After complete closure of the ASD and postoperative long-term oral prostacyclin (PGI2) therapy, pulmonary artery peak pressure decreased from 110-72 (mean 84) to 105-45 (mean 74) mmHg immediately after operation and 65-40 (mean 57) mmHg after PGI2 therapy. The New York Heart Association functional status of the patients improved from class II-III to class I with oral PGI2 only. Our cases demonstrate that despite more than 70% occlusion of the small pulmonary arteries and arterioles, surgery and long-term PGI2 therapy can reduce pulmonary artery pressure and improve the quality of life.