The factors determining complications after pancreaticoduodenectomy (PD) have not yet been identified clearly. This retrospective study examined, using reproducible classification systems, the type and severity of complications as well as the factors to predict them.Between 1998 and 2005 PD was performed in 351 consecutive patients with peri-ampullary tumours. Logistic regression models were used in univariate as well as in corrected, multivariate analyses in order to identify the optimally combined factors related to the occurrence of post-operative complications.Post-operative complication rate was 50.7%, mortality 3.1% and re-operation rate 7.1%. Pancreatic fistula (12%) was responsible for higher mortality (9.5%; p=0.011) and re-operation (30.9%; p<0.001) rates. Hospital length of stay (LOS) was (p<0.001) longer for patients with post-operative complications (median 21.5 (range 1-128) vs. 14 (7-42) days) or pancreatic fistula (28.5 (8-128) vs. 17 (1-63) days), and related to the severity of complications. Surgeon (Odds ratio [OR] 2.03; confidence interval [CI] 1.20-3.41; p=0.008), male gender (OR 1.72; CI 1.05-2.81; p=0.032), and pre-operative hyperbilirubinaemia (OR 1.04; CI 1.001-1.08; p=0.046) were independent risk factors for post-operative complications. Neither prophylactic octreotide nor pre-operative biliary drainage improved post-operative outcome.Surgeon, male gender, and pre-operative hyperbilirubinaemia determine complication rate following PD. Pancreatic fistula is the most common complication and is associated with increased mortality, re-operation rate and LOS.