Objectives: To investigate the clinical value of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1 alpha (HIF-1 alpha) in diagnosing malignant and tuberculous pericardial effusion. Methods: Eighty patients with exudative pericardial effusion undergoing pericardiocentesis and drainage were divided into 2 groups, namely those with malignancy and those with tuberculosis. The levels of HIF-1 alpha, VEGF, lactate dehydrogenase (LDH) and adenosine deaminase (ADA) in pericardial fluid and serum were measured. Routine and cytological examination of pericardial fluid, clinical characteristics and some blood parameters were compared between the 2 groups. Results: There were 33 patients with tuberculous pericardial effusion and 47 with malignant pericardial effusion. The levels of VEGF and HIF-1 alpha in pericardial fluid in the malignancy group were significantly higher than those in the tuberculosis group (p < 0.01), and there was a moderate positive correlation between the levels of VEGF and HIF-1 alpha (r = 0.79, p < 0.01). The sensitivity and specificity of combining VEGF and HIF-1 alpha were 90.8 and 88.3%, respectively. The 2 groups showed no differences with regard to gender distribution, occurrence of fever, erythrocyte sedimentation rate or the levels of hemoglobin, LDH, ADA, serum HIF-1 alpha and VEGF. Conclusions: Both VEGF and HIF-1 alpha in pericardial fluid have determinative value in the differential diagnosis of malignant and tuberculous pericardial effusion. Copyright (C) 2010 S. Karger AG, Basel