Irreversible pulmonary arterial hypertension is considered a contraindication for surgical or percutaneous closure of atrial septal defects (ASD) due to risk of right heart failure. We present a case of 37 years-old woman who was referred to our center due to progressive worsening fatigue and high probability of pulmonary hypertension on a transthoracic echocardiogram. The diagnostic work-up revealed the presence of an ostium secundum atrial septal defect and severe pre-capillary pulmonary hypertension on right heart cathetherization (RHC). The patient was considered inoperable and started medical therapy with sildenafil and bosentan. After one year of treatment, she repeated RHC that showed a significant reduction in pulmonary vascular resistance making her eligible for closure. Surgical closure of ASD with a fenestra was performed with success. Our case emphasizes the importance of individual assessment even if cases where initial evaluation is unfavorable to closure in accordance with the guidelines.