PURPOSE: To evaluate the accuracy and safety of ultrasound-guided biopsy of the thickened peritoneal reflections and to determine the efficacy and diagnostic role of this procedure in the differential diagnosis of peritoneal tuberculosis and peritoneal carcinomatosis. MATERIALS AND METHODS: Twenty-seven patients with only mildly thickened (25 mm or less) peritoneal reflections without apparent mass formations, and in whom imaging findings were not diagnostic, underwent ultra-sound-guided biopsy. Five-MHz linear or convex linear array transducers were used for ultrasound guidance,and an automated gun with 18-gauge (n = 23) or 20-gauge (n = 4) needles for tissue sampling. Biopsies were performed on the thickened parietal peritoneum (n = 9), greater omentum (n = 11), and small bowel mesentery (n = 7), and the results were compared with the final diagnosis determined by adiologic/clinical follow-up (n = 17) or laparoscopic biopsy (n = 10). Complications and changes in hemoglobin and hematocrit levels after the procedure were evaluated. RESULTS: Specimens adequate for pathologic examination were obtained in all 27 patients. The histopathologic results were metastatic carcinomatosis (n = 15), peritoneal tuberculosis (n = 8), and chronic granulomatous inflammation (n = 4). Specific pathologic diagnosis was obtained in all patients except the four with chronic granulomatous inflammation. Differentiation between benignancy and malignancy was possible in all patients and the histopathologic specific accuracy rate was 100%. No clinically significant complications were observed. In 24 patients with ascites at the site of the biopsy, transient bleeding was observed immediately after the procedure, but this stopped spontaneously within a few minutes. Post-procedural hemoglobin and hematocrit levels were only minimally lower (mean values of 0.9g/dL and 3.0%, respectively) than pre-procedurally. CONCLUSION: Ultrasound-guided biopsy of thickened peritoneal reflections is a safe and effective diagnostic procedure and is useful in the differential diagnosis of peritoneal tuberculosis and peritoneal carcinomatosis.