Stapling is a popular method for stump closure in distal pancreatectomy (DP). However, research on which cartridges are suitable for different pancreatic thickness is lacking. To identify the optimal stapler cartridge choice in DP according to pancreatic thickness.From November 2011 to April 2015, data were prospectively collected from 217 consecutive patients who underwent DP with 3-layer endoscopic staple closure in Seoul National University Hospital, Korea. Postoperative pancreatic fistula (POPF) was graded according to International Study Group on Pancreatic Fistula definitions. Staplers were grouped based on closed length (CL) (Group I: CL ≤ 1.5 mm, II: 1.5 mm < CL < 2 mm, III: CL ≥ 2 mm). Compression ratio (CR) was defined as pancreas thickness/CL. Distribution of pancreatic thickness was used to find the cut-off point of thickness which predicts POPF according to stapler groups.POPF developed in 130 (59.9%) patients (Grade A; n = 86 [66.1%], B; n = 44 [33.8%]). The numbers in each stapler group were 46, 101, and 70, respectively. Mean thickness was higher in POPF cases (15.2 mm vs 13.5 mm, P = 0.002). High body mass index (P = 0.003), thick pancreas (P = 0.011), and high CR (P = 0.024) were independent risk factors for POPF in multivariate analysis. Pancreatic thickness was grouped into <12 mm, 12 to 17 mm, and >17 mm. With pancreatic thickness <12 mm, the POPF rate was lowest with Group II (I: 50%, II: 27.6%, III: 69.2%, P = 0.035).The optimal stapler cartridges with pancreatic thickness <12 mm were those in Group II (Gold, CL: 1.8 mm). There was no suitable cartridge for thicker pancreases. Further studies are necessary to reduce POPF in thick pancreases.