BACKGROUND: Resection of the caudate lobe of the liver is technically demanding, with the disparate goals of preserving major vascular and biliary structures without compromising tumor clearance. Our objective was to assess our results with resection of the caudate lobe of the liver for malignant disease. STUDY DESIGN: From 1992 to 2004, we performed caudate resection for malignancy in 150 patients. Clinicopathologic correlates, surgical methods, patterns of recurrence, and survival were analyzed. RESULTS: Of the 150 patients identified, 21 (14%) underwent an isolated caudate lobe resection and 129 (86%) underwent caudate lobe resection as part of a more extensive hepatectomy. The most common indication was for metastatic colorectal cancer (48%), followed by cholangiocarcinoma (30%) and hepatocellular cancer (10%). Thirty patients required resection and reconstruction of the portal vein (n = 16), vena cava (n = 15), or both. Pathologic microscopic margins were positive in 30 patients (20%). At least one postoperative complication was reported in the majority of patients (55%), and nine patients (6%) died as a result of these complications. Postoperative mortality was significantly higher in patients who underwent a major vascular reconstruction (20% versus 2.5%, p < 0.002). Median survivals for patients with colorectal metastasis, cholangiocarcinoma, and hepatocellular carcinoma were 37, 28, and 32 months, respectively. CONCLUSIONS: Performing caudate hepatectomy with negative microscopic margins remains a technical challenge because of the proximity of major biliary and vascular structures. Although caudate resection of the liver can be performed safely, concomitant major vascular reconstruction substantially increases the mortality of the procedure.