Background: The use of neoadjuvant preoperative chemoradiotherapy CRT for pancreatic cancer has been advocated for its potential ability to optimize patient selection for surgical resection and to downstage locally advanced tumors. This article reports our experience with neoadjuvant CRT for localized pancreatic cancer. Methods: Since 1995, 111 patients with radiographically localized, pathologically confirmed pancreatic adenocarcinoma have received neoadjuvant external beam radiation therapy EBRT; median, 4500 cGy with 5-flourouracil–based chemotherapy. Tumors were defined as potentially resectable PR, n = 53 in the absence of arterial involvement and venous occlusion and locally advanced LA, n = 58 with arterial involvement or venous occlusion by CT. Results: Five patients 4.5% were not restaged due to death n = 3 or intolerance of therapy n = 2. Twenty-one patients 19% manifested distant metastatic disease on restaging CT. Twenty-eight patients with initially PR tumors 53% and 11 patients with initially LA tumors 19% were resected after CRT. Histologic examination revealed significant fibrosis in all resected specimens and two complete responses. Surgical margins were negative in 72%, and lymph nodes were negative in 70% of resected patients. Median survival in resected patients has not been reached at a median follow-up of 16 months. Conclusions: Neoadjuvant CRT provided an opportunity for patients with occult metastatic disease to avoid the morbidity of resection and resulted in tumor downstaging in a minority of patients with LA tumors. Survival after neoadjuvant CRT and resection appears to be at least comparable to survival after resection and adjuvant postoperative CRT.