Although surgical procedures that improve pancreatic drainage alleviate abdominal pain in the vast majority of patients with chronic pancreatitis, postoperative absorption and nutritional status are less predictable. The present study was designed to determine the efficacy of pancreatic enzyme supplementation in maintaining postoperative digestion and nutrition in patients who had received the local resection-longitudinal pancreaticojejunostomy (LR-LPJ) procedure for chronic pancreatitis. We evaluated nutritional status and intestinal absorption in 11 patients who had undergone LR-LPJ. The efficacy of postoperative pancreatic enzyme supplementation was studied by measurements of intestinal absorption and nutritional status at baseline, after 4 weeks of individualized daily dosage of pancreatin (Creon), and after an additional 4 weeks of randomization to receive another 4 weeks of pancreatin or placebo. All patients demonstrated abnormal digestion of fat, protein, and total energy at baseline 3 weeks after surgery. Pancreatin supplementation significantly improved the coefficients of absorption of dietary fat and total energy over the next 4 weeks. Between 4 and 8 weeks, pancreatin significantly improved protein absorption and nitrogen balance, whereas placebo substitution worsened the absorption of dietary fat and total energy. Nutritional status was not significantly altered over the 8-week study period, although four patients receiving pancreatin gained more than 3.6 kg body weight. The data suggest that long-term postoperative pancreatic enzyme supplementation is both efficacious and necessary in chronic pancreatitis patients after LR-LPJ.