Background: D-dimer level marker of solid phase fibrin dissolution is found to be high in patients with exudative pleural effusion. This study aimed to compare between D dimer concentration pleural effusions in order to investigate the predictor value of D dimer to differentiate the cause of pleural effusion. Methods: This observational descriptive cross sectional study was carried out in Chest department at Zagazig University Hospitals on 108 patients with pleural effusion. The diagnosis of pleural fluid is based on radiological base (chest x-ray and/or CT when needed, chest ultrasonography) and thoracocentesis of pleural fluid analysis for (biochemical, bacteriological and cytological examination), Thoracoscopy and pleural biopsy was done for patients not diagnosed and laboratory investigations measurement of serum and pleural fluid D-dimer level by ELFA-ELISA. Results: There was high statically significant Pleural D- dimer, Serum D- dimer value, in exudate compared to transudate pleural effusion, p<0.05.at cut of value pleural d dimer (≥3.5ug/dl): show sensitivity 100%, specificity 92.9% and accuracy 98.1% and Serum D-dimer at cut of value (≥2.4ug/dl): show sensitivity 73.8%, specificity 78.6% and accuracy 75% (p<0.05) in exudate compared to transudate effusion. The findings also demonstrate a higher significancy in both Pleural D-dimer and Serum D-dimer value in pleural effusion due to malignant, when it compared to other exudative pleural effusion (p<0.05). Conclusion: The level of pleural D -dimer at cut off value 3.5 ug/dl can differentiate between transudate and exudate and may differentiate between malignant and non malignant effusion at cut off value 5 ug/dl.