Periampullary tumors are highly malignant masses with poor prognosis. Surgical resection is the only treatment for patients with this disease. The preoperative evaluation of masses is essential to determine the tumor resectability and vascular invasion. The aim of this study was to determine the diagnostic accuracy of 64-slice multi-detector computed tomography (MDCT) in detecting the resectability of periampullary masses. A cross-sectional study was conducted on patients with a definite diagnosis of periampullary cancer. All the participants underwent an MDCT scan before the surgical pancreaticoduodenectomy. The preoperative results were compared to the intraoperative findings and the diagnostic accuracy was determined based on the sensitivity and specificity of the MDCT. From June 2015 until June 2016, 32 patients with periampullary carcinoma were enrolled in the study. Of 32 masses, one of them considered nonresectable because of the gross vascular invasion in th CT images. After the operation, the overall resectability rate was 81.3%. The sensitivity and specificity of MDCT for tumor resectability was 100% and 16.7%, respectively, with an overall accuracy of 84.4%. To sum up, MDCT had high sensitivity but low specificity in the preoperative evaluation of preampullary carcinomas. The low specificity resulted from the low accuracy of the CT scan in detecting vascular involvement.