The operative mortality and morbidity of pancreaticoduodenectomy (PD) remain high. We analyzed PD patients' clinical characteristics and surgical outcomes and discuss how PD clinical outcomes could be improved. We retrospectively reviewed the cases of 400 patients who underwent a PD between January 1998 and April 2014 at Okayama University Hospital, a very-high-volume center. We identified and compared the clinical outcomes between two time periods (period 1: 1998-2006 vs. period 2: 2007-2014). The total postoperative mortality and major complication rates were 0.75% and 15.8% , respectively, and the median postoperative length of stay (LOS) was 32 days. Subsequently, patients who underwent a PD during period 2 had a significantly shorter LOS than those who underwent a PD during period 1 (29 days vs. 38.5 days, p＜0.001). The incidence of mortality and major complications did not differ between the two periods. In our multivariate analysis, period 1 was an independent factor associated with a long LOS (p＜0.001). The improvement of the surgical procedure and perioperative care might be related to the shorter LOS in period 2 and ot the consistently maintained low mortality rate after PD. The development of multimodal strategies to accelerate postoperative recovery may further improve PD's clinical outcomes.