Background: The diagnosis of malignant ascites can be difficult. The overall sensitivity of cytology smears for the detection of malignant ascites is 58%–75%. There is a debate about the role of ascitic fluid lipids and their gradients in the differential diagnosis of ascites. This study aims to evaluate the role of ascitic fluid lipids and their gradients in the differentiation of malignant ascites from cirrhotic ascites. Patients and Methods: Ninety‑six patients were enrolled in this study divided into two groups according to the cause of ascites; Group I: included 48 patients with malignant ascites and Group II: included 48 patients with cirrhotic ascites. Results: Ascitic fluid cholesterol, triglycerides, and phospholipids were significantly higher among patients of Group I (77.5 ± 11.5, 82.4 ± 17.04 mg/dl, and 0.92 ± 0.14 mmol/L vs. 27.7 ± 7.5, 56.2 ± 16.2 mg/dl, and 0.33 ± 0.09 mmol/L in succession P < 0.001). The cutoff values of cholesterol, triglycerides, and phospholipids were (41.5, 62.5 mg/dl and 0.45 mmol/L successively); they can predict the presence of malignant ascites with sensitivity of (100, 87, and 100% successively) and with specificity of (97.9, 60.4, and 87.5% successively). Conclusion: Ascitic fluid lipids are valuable markers in the differentiation of malignant ascites from cirrhotic ascites.