BACKGROUND: Pancreatic fistula (PF) is a major source of morbidity after pancreatectomy. The International Study Group on Pancreatic Fistula (ISGPF) defines postoperative fistula by an amylase concentration in the abdominal drain of more than three times the serum value on day 3 or more after surgery. However, this definition fails to identify some clinical fistulas. This study examined the association between lipase measured in abdominal drainage fluid and PF. METHODS: Amylase and lipase levels in the abdominal drain were measured 3 days after pancreatic resection. Grade B and C fistulas were classified as clinical fistulas, regardless of whether the measured amylase concentration was considered positive or negative. The PF group included patients with a clinical fistula and/or those with positive amylase according to the ISGPF definition. RESULTS: Sixty-five patients were included. The median level of lipase was higher in patients with positive amylase than in those with negative amylase: 12 176 versus 64 units/l (P < 0*001). The lipase level was 16 500 units/l in patients with a clinical fistula and 224 units/l in those without a clinical fistula (P = 0*001). Patients with a PF had a higher lipase concentration than those without: 7852 versus 64 units/l (P < 0*001). A lipase level higher than 500 units/l yielded a sensitivity of 88 per cent and a specificity of 75 per cent for PF. For clinical fistulas the sensitivity was 93 per cent and specificity 77 per cent when the threshold for lipase was 1000 units/l. CONCLUSION: Lipase concentration in the abdominal drain correlated with PF. A threshold of 1000 units/l yielded a high sensitivity and specificity for the diagnosis of clinical PF. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.