Background: Pleural effusion is a common and increasing problem, however, its diagnosis remains a challenge due to its diverse etiologies, so this research was done to assess the value of ultrasonography in differentiation between benign and malignant pleural effusion at Chest Department at Zagazig University hospitals. Patients and Methods: This prospective cross section study was carried out at Chest department and Radiology department, Zagazig University Hospitals in the period from January 2023 till June 2023. This study included 60 patients with suspected malignant pleural effusion. Chest x-ray, CT Chest, Thoracic ultrasound, were performed for all patients. Results: Chest X ray findings revealed that 66.7% of patients had right-side lesion and 31.7% had massive effusion. CT findings revealed that 31.7% had massive effusion, 65% had pleural thickening, three patients had hilar mass, one patient had pulmonary nodule and one patient had cavity lesion. Four patients had mediastinal lymphadenopathy (6.7%). Chest US examination of patients revealed that 30% had massive effusion, 21.7% had septation, 41.7% had nodule, and 41.7% had pleural thickening. US picture suggested benign nature of lesion in 48.3% of patients. Pelvi-abdominal US revealed that 55% of patients were free and 13.3% had mild hepatomegaly. Neck US revealed that 80% of patients were free and 11.7% had enlarged cervical lymphadenopathy. There is statistically significant relation between type of lesion and presence of septation (53.8% of patients with septation had benign lesion), and nodules. Ultrasound can diagnose malignant lesion among 29 patients out of 48 patients with confirmed malignancy with sensitivity 60.4% and benign lesion in US can rule out malignancy in 10 out of 12 patients with confirmed benign lesions with specificity 83.3%. Positive and negative predictive value were 34.5% and 93.6% respectively with overall accuracy 65%. There is highly significant difference between benign and malignant pleural effusion regarding absence of septation (by ultrasonography) as it can diagnose malignant lesion among 42 patients out of 48 patients with confirmed malignancy with sensitivity 87.5% and septation can rule out malignancy in 7 out of 12 patients with confirmed benign lesions with specificity 58.3%. Positive and negative predictive value were 89.4% and 53.9% respectively with overall accuracy 81.7% Conclusion: Ultrasound is a simple and safe technique that can be a good tool for diagnosis of malignant pleural effusion