Introduction: Patients with adenocarcinoma of the pancreas have long-term survival of less than 15%. Previous studies have documented worse overall survival in patients undergoing resection with positive margins. Most of these studies have included both R1 and R2 resections. The impact of a R1 (microscopic) resection margin in patients receiving chemoradiation is not clear. Methods: Our pancreas database was queried for patients undergoing pancreaticoduodenectomy for adenocarcinoma between January 2002 and August 2006. All operative specimens were analyzed to determine the status of their pancreas, bile duct and retroperitoneal margins. Standard demographic, clinicopathologic, and outcome variables were recorded. All patients were divided into either margin negative (R0) or microscopically positive (R1) resections. Standard statistical calculations were performed. Results: Over the study period 80 patients underwent pancreaticoduodenectomy for adenocarcinoma. Of these only 42 patients (12 males, 30 females), completed adjuvant chemoradiation. 29 patients underwent a R0 resection and 13 patients were found to have microscopic positive margin (R1). Patients with grossly positive margins (R2) were excluded from analysis. Positive margins included the retroperitoneal margin (n=8), and pancreas margin (n=5). There were no differences between the two groups with respect to age, sex, race, tumor grade, T-stage or angiolymphatic invasion. Patients undergoing a R1 resection had an increased local recurrence rate (42% vs 4%, p=0.01). A single patient who underwent a R0 resection had a local recurrence 23 months following surgery, while the median time to local recurrence for the R1 group was 8 months. There were no differences in overall survival between R1 and R0 resections. Conclusion: Margin positivity can be due to either surgical technique or tumor biology. Despite chemoradiation, an increased recurrence rate was seen in patients with microscopic positive margins, although this did not impact overall survival. Future clinical trials need stratification for margin status when analyzing novel adjuvant therapies.