Background: Pulmonary arterial hypertension (PAH) is a frequent consequence of untreated congenital heart disease (CHD). Elevated pulmonary pressure induces vascular remodeling and RV dysfunction through several mechanisms, culminating in a gradual elevation in pulmonary vascular resistance (PVR) and ultimately reversal of shunt with the progression of Eisenmenger syndrome. Objectives: To analyze the role of matrix metalloproteinase 2 (MMP-2) in pulmonary hypertension (PH) due to CHD and also to investigate if this marker has a diagnostic or prognostic value. Subjects and Methods: 25 subjects with PAH associated with CHD, 25 subjects with CHD without PH, and 25 healthy children as controls were included. Heart electrocardiography, Doppler and Two-dimensional, M-mode echocardiographic evaluation of CHD and pulmonary pressure were done. Blood specimens were collected from all subjects to assess serum MMP-2 levels by ELISA. Results: The mean MMP-2 values significantly enhanced in PAH-CHD children as compared to CHD without PAH patients and controls (P<0.05). A significant correlation was found among MMP-2 and mean pulmonary artery pressure (mPAP) and echocardiographic parameters of RV diameter and function. Sensitivity of MMP-2 as a diagnostic marker was 52% and specificity was 96%. Conclusion: Serum MMP-2 were significantly enhanced in PAH-CHD children and were correlated to severity of PH and to the echocardiographic measures of its assessment. MMP-2 could be used as an excellent diagnostic and predictive biomarker in PAH-CHD children, which could be beneficial in treatment of PH in children and prediction of their outcome.