Aim: To evaluate the efficacy of a novel hydrogel sheet in preventing postoperative pancreatic fistula (POPF). Background: Postoperative pancreatic fistula is a life-threatening complication. As no study has reported the use of hydrogel sheets in preventing POPF, their effectiveness for that purpose remains unclear. Methods: A novel hydrogel sheet made of polyvinyl alcohol (PVA) was prepared by the freeze-thaw method. The pancreatic ducts and surrounding pancreatic parenchyma of rats were transected to induce a pancreatic fistula. Next, the sheet was attached to the transection site. Ascitic fluid amylase and lipase concentrations were measured. Neoveil®, a nonwoven polyglycolic acid (PGA) felt, is already clinically used as an absorbable reinforcing material at pancreatic transection sites. Neoveil® was used for comparison, as was VIEWGEL®, which is marketed as a wound dressing. Results: The hydrogel sheet remained in place 48 hours postoperatively. The ascitic amylase concentrations in the control, VIEWGEL®-treated, Neoveil®-treated, and hydrogel-treated rats, respectively, were 4992.4 ± 5355.7, 1068.4 ± 269.1, 730.2 ± 425.2, and 303.1 ± 240.1 IU/L; the ascitic lipase concentrations were 2279.8 ± 3395.2, 169.5 ± 100.6, 90.4 ± 71.0, and 86.8 ± 59.8 IU/L. The ascitic amylase and lipase levels were significantly lower in the hydrogel group than in the other groups (P <.05). Conclusions: This novel hydrogel sheet effectively prevents pancreatic fistulas and has promising clinical application potential.