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Objective To evaluate the efficacy of transanastomotic pancreatic duct internal stenting in the reduction of postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy. Design Retrospective study. Setting Mayo Clinic. Patients Between January 1, 1999, and September 30, 2010, 553 patients underwent pancreaticoduodenectomy by a single surgeon. Main Outcome Measures Rates of POPF, morbidity, and mortality between stent and no-stent groups. Results The clinically relevant POPF (International Study Group on Pancreatic Fistula definition grade B or C) rates in the stent and no-stent groups were similar (9.6% [43 of 449 patients] and 12.5% [13 of 104 patients], respectively; P = .38). Postoperative outcomes and morbidity were also similar between the 2 groups. Mortality was 0.7% (3 of 449 patients) for the stent group and 1.0% (1 of 104 patients) for the no-stent group. Four patients (0.9%) required endoscopic retrieval of the anastomotic stent. In subset analysis, the clinically relevant POPF rates in patients with a small pancreatic duct (≤3 mm; n = 167) were similar in the stent and no-stent groups (17.7% [23 of 130 patients] and 24.3% [9 of 37 patients], respectively; P = .38). In patients with a soft pancreatic gland (n = 64), rates of clinically relevant pancreatic fistulae were also similar in the stent and no-stent groups (31.7% [13 of 41 patients] and 17.4% [4 of 23 patients], respectively; P = .20). Conclusions Internal transanastomotic pancreatic duct stenting does not decrease the frequency or severity of POPF. The effect of stenting on long-term anastomotic patency warrants further investigation.