One of the most common complications after distal pancreatectomy is a fistula from the pancreatic remnant. Factors influencing the development of a pancreatic fistula after distal pancreatectomy have not been clearly elucidated. The records of 91 patients who underwent distal pancreatectomy for chronic pancreatitis between 1995 and 2003 were retrospectively reviewed and analyzed. Average daily volume and amylase concentration between postoperative days 2 and 20 from drains located at the pancreatic resection site were compared to clinical variables. Out of 137 pre- and intraoperative clinical variables, multivariate analysis showed serum creatinine (t = 3.05, p = 0.004), history of intraabdominal operation (t = -2.68, p = 0.01), right-sided pancreatic duct dilation (t = 2.65, p = 0.01), synchronous cholecystectomy (t = 2.53, p = 0.02), and serum albumin (t = -2.19, p = 0.04) to be independently associated with drain volume. Drain amylase concentration was linked to serum creatinine (t = 8.55, p < 0.001), blood urea nitrogen (t = -3.43, p = .001), preoperative parenteral nutrition (t = 2.56, p = .01), and serum alkaline phosphatase (t = 2.51, p = 0.01). There was no correlation between the degree of fibrosis and drain output. Technique of pancreatic transection and presence of suture closure of the pancreatic duct did not affect drain output. In conclusion, the amount and amylase concentration of postsurgical drainage after distal pancreatectomy for chronic pancreatitis is dependent on markers of renal dysfunction, malnutrition, biliary disease, and possibly inflammation. These factors, if medically reversible, should be addressed in patients who are candidates for distal pancreatectomy for chronic pancreatitis.