Introduction: What impact does pancreaticoduodenectomy (PD) have on exocrine function? Does the pancreatic anastomosis remain patent? When stool elastase became available for testing in November 2001 we began preoperative assessment and then increasingly employed postoperative measurements. Patients: From 11/2001 until 11/2005, 171 patients underwent PD by the same surgeon. Preoperative stool elastase was measured in 122 (71%) and was repeated postoperatively at 3 ± 1 mo, 12 ± 2 mo, and 24 ± 3 mo. At the same time periods an abdominal CT scan was used to assess patency of the pancreatic anastomosis as implied by lack of pancreatic duct dilation in the remnant ("dilation" = duct >3mm or, if duct dilated preop, then duct that failed to decrease in size). Indications for PD in the 122 cases were pancreatic cancer (20%), other periampullary tumors (19%), cystic tumors (39%), chronic pancreatitis (19%), and other (2%). PD was pylorus-preserving in 93%. All cases were reconstructed with duct-to-mucosa pancreaticojejunostomy. Stool elastase was expressed as normal (> 200 µg/gram stool), moderately reduced (100-200 µg/g), or severely reduced (<100 µg/g). Results: Preoperative stool elastase values were “normal” in 69% (pancreatic cancer 40% normal vs. all other groups >76% normal, p≤0.001). Preoperative values were then compared to post-PD levels to assess if the patient maintained their pre-PD level (table). The CT scans at the time of the 64 stool elastase measurements after PD were examined for pancreatic duct dilation in the pancreatic remnant. Duct dilation was observed in 13% (4/30) where elastase levels had been “reduced” after PD versus 4% (1/27, not significant) in the group with stool elastase "increased" or "maintained." Conclusions: Based on stool elastase one-third of patients about to have PD will have exocrine insufficiency; an observation most common among the patients with pancreatic cancer (60%). After PD, levels of stool elastase are further depressed in the majority of cases probably from parenchymal loss since we could not implicate an occluded pancreatic anastomosis. After PD exocrine supplementation should be given to at least all patients with pancreatic cancer, especially those with impending adjuvant therapy. To further improve the long-term results after PD each surgeon should assess the effect of their own type of pancreatico-enteric technique on exocrine function.