A retrospective study of patients with surgically resectable adenocarcinoma of the pancreatic head was undertaken to determine which prognostic factors are independently associated with improved survival. Thirty-four men and 41 women (mean age, 61.9 years) had resection for adenocarcinoma of the pancreatic head between 1980 and 1997 at Rush- Presbyterian-St. Luke's Medical Center. Surgical resections included 15 total pancreatectomies, 43 pyloric-preserving procedures, and 17 standard Whipple procedures. Thirty-six patients received adjuvant radiation and/or chemotherapy. Overall median survival was 13 months, with a 5-year survival of 17 per cent. Thirty-day surgical mortality was 1.3 per cent. Significant factors that negatively influenced survival using univariate Kaplan-Meier analysis were: positive resection margin (P = 0.01), intraoperative blood transfusion (P = 0.01), and lymph node metastases (P = 0.01). Presenting signs and symptoms, patient demographics, operative procedure, tumor size, histologic differentiation, and adjuvant therapy did not have a significant impact on survival. Using multivariate Cox regression analysis, the only significant independent factors improving survival were the absence of intraoperative blood transfusion (P = 0.02) and a negative resection margin (P = 0.04). Performing pancreaticoduodenectomy for adenocarcinoma of the head of the pancreas with negative microscopic margins of resection and without intraoperative transfusion significantly improves survival.