The aim of the study was to perform a comprehensive analysis of patients with a benign final histology after pancreaticoduodenectomies (PD) for suspected pancreatic and periampullary cancer.Material and methods. We searched the pathology database at the King's College Hospital for negative PD specimens submitted between January 2004-December 2010. Clinical, diagnostic, surgical, histopathological and outcome data were collected retrospectively. Pathology specimens and imaging results have been re-evaluated. A literature review was performed to identify factors affecting the incidence across centres.Results. 469 PD were performed for presumed cancer. The incidence of benign disease encountered in this group was 7.25% (34/469). Autoimmune pancreatitis (AIP) was a finding in 26.47% (9/34) of cases. 17.65% of PD were complicated by a pancreatic leak and the overall mortality rate was 8.82% (3/34). Radiologists revised over 75% of pre-operative diagnoses. The incidence of benign disease was correlated with the overall centre experience and utilisation of CT imaging, but not ERCP or EUS. Conclusions. It is impossible with current diagnostics to entirely avoid cases of benign disease in patients undergoing PD for suspected cancer. The mortality rate is higher in this group, but it is possible to avoid unnecessary procedures in experienced centres. AIP represents an important diagnostic entity, which should be actively pursued pre-operatively.