BACKGROUND: Persistent pulmonary hypertension of the neonate (PPHN) is a serious disorder. The long pentraxin 3 (PTX3) plays an important role in angiogenesis, cell proliferation, tissue repair and cell regulation. The present study aims to assess the diagnostic and clinical value of PTX3 in PPHN. METHODS: The present case-control 60 full-term neonates diagnosed with PPHN by echocardiography within 72 hours of birth. In addition, there were 30 age and sex-matched healthy neonates who served as controls. All participants were subjected to careful history taking and complete clinical examination, Laboratory investigations included complete blood count, C-reactive protein (CRP), blood culture and PTX3 level. Radiological investigations included plain X- ray and two-dimensional transthoracic echocardiography (TTE). RESULTS: Comparison between patients and controls revealed that patients had significantly higher CRP (6.12±2.18 versus 3.69±1.25 mg/dl, p < 0.001) and PTX3 levels (2.07±0.67 versus 0.96±0.21, p < 0.001) when compared with controls. Patients with associated PDA had significantly higher PTX3 levels when compared with patients without (2.58±0.5 versus 2.02±0.51 ng/ml, p = 0.002). Also, patients with associated PFO had significantly higher PTX3 levels when compared with patients without (2.12±1.05 versus 2.05±0.46, p = 0.002). ROC curve analysis identified good performance of CRP and PTX3 levels in diagnosis of PPHN with PTX3 showing better performance. CONCLUSIONS: There is a significant association between serum PTX3 levels and PPHN particularly those with associated PDA or PFO.