To study the accuracy of preoperative staging techniques for assessing resectability of pancreatic and ampullary adenocarcinoma, we entered 88 consecutive candidates into a prospective study of contrast-enhanced computed tomography, magnetic resonance imaging, angiography, and laparoscopy. Resectability was proved in 16 (29%) of 55 patients for the head of the pancreas, 1 (6%) of 17 for the body and tail of the pancreas, and 14 (88%) of 16 for the ampulla. The combined findings of computed tomography and angiography showed that more than 87% of pancreatic head tumors were unresectable because of vascular encasement, but neither modality sufficed alone. Small liver and peritoneal metastases were found in 15 (27%) of 55 cancers of the head of the pancreas, 11 (65%) of 17 cancers of the body and tail of the pancreas, and 1 (6%) of 16 cancers of the ampulla; computed tomography missed all but 2 of these instances of metastasis, but laparoscopy with biopsy identified 22 (96%) of 23 instances. Magnetic resonance imaging findings did not differ significantly from computed tomography and conferred no added benefit. Ninety percent of unresectable tumors were identified. Seventy-eight percent of pancreatic head cancers were resectable when all test results were negative vs 5% (2/37) when any test result was positive. This study demonstrates that accurate and efficient triage is possible for patients with cancer of the pancreas and ampulla.