Objective. Previous studies have identified a significant volume–outcome relationship for hospitals performing pancreaticoduodenectomy (PD). However, scant information exists concerning the effects of increased caseload of PD within the same hospital. Here, we describe the effects of becoming a high-volume provider of PD. Material and methods. The study group comprised 221 patients who underwent PD between 2000 and 2012. Hospital volume was allocated into three groups: low-volume (<10 PDs/year), years 2000–2004, n = 25; medium-volume (10–24 PDs/year), years 2005–2009, n = 86; and high-volume (≥25 PDs/year), years 2010–2012, n = 110. Results. The annual number of PDs increased from 5 in 2000 to 39 in 2012. The median operative duration decreased over the volume categories (p < 0.001). Intraoperative blood loss dropped (p < 0.001). The need for intraoperative blood transfusion was reduced (p < 0.001). Increasing hospital volume was associated with fewer reoperations (p = 0.041) and shorter postoperative length of stay (p = 0.010). There was a tendency toward reduced mortality: 4.0% for the low-volume period, 2.3% for the medium-volume period, and 0% for the high-volume period (p = 0.066). Conclusions. The transition from a low- to a high-volume center resulted in optimized outcomes for PD and 0% operative mortality, favoring the continued centralization of this high-risk operation.