Background: CT scanning and mesenteric angiography are insensitive tests for diagnosing vascular invasion by pancreatic cancer. Endoscopic ultrasound (EUS) has been proposed as an alternative. The sensitivity, specificity, and accuracy of specific EUS criteria for diagnosing malignant invasion of the branches of the portal venous system have not been determined. Methods: This is a prospective blinded evaluation of EUS and angiography to diagnose malignant invasion of the portal venous system by pancreatic cancer in 45 patients, 28 of whom underwent surgery. Surgical staging was used as the gold standard for determining the accuracy of EUS and angiography. Results: Four EUS criteria were studied and the overall accuracy rates were as follows: irregular venous wall (87%), loss of interface (78%), proximity of mass (73%), and size (39%). Although “irregular venous wall” was the most accurate, it suffered from a low sensitivity rate (47%) because of its relative inability to detect superior mesenteric vein invasion (sensitivity of 17%). The angiographic criteria had accuracy rates of 73% to 90% with low sensitivity rates (20% to 77%). The clean resection rate was 86% when all tests were used, 78% if EUS was used without angiography, and 60% if only angiography was used. Conclusion: EUS is highly sensitive for detecting portal and splenic vein invasion by pancreatic cancer, but may be insensitive for superior mesenteric vein involvement. (Gastrointest Endosc 1996;43:561-7.)