Meta-analysis of 10 randomized prospective trials demonstrated a higher risk of postoperative bleeding from pancreaticogastrostomy (PG) compared with pancreatojejunostomy following pancreatoduodenectomy (PD). This study evaluated the incidence, risk factors, and treatment of anastomotic bleeding from invaginated PG. We retrospectively evaluated all consecutive PDs performed between April 1, 2011 and December 31, 2022 using invaginated PG by the double purse-string technique. Multivariate analysis identified risk factors for anastomotic PG bleeding. During the study, 695 consecutive patients with a median age of 66 years underwent PD; the majority was performed for ductal pancreatic adenocarcinomas. Simultaneous vascular resections were performed in 328 patients. Postoperative mortality was 4.1%. Bleeding from PG occurred in 33(4.6%) patients at a median interval of 5 days (range, 1-14) from surgery, leading to reoperation in 21(63%). PG bleeding-related mortality was 9.0%. Multivariate analyses identified a soft pancreatic texture and Wirsung duct > 3 or ≤ 3mm (Class C and D, respectively, of the ISGPS) (odds ratio [OR]: 2.17, 95% confidence interval [95% CI]: 1.38-3.44; P = 0.0009) and wrapping of the invaginated pancreas (OR: 0.37, 95% CI: 0.17-0.84; P = 0.01) as independent risk factors for PG bleeding. In a large volume setting, anastomotic bleeding from invaginated PG occurred in ~ 5% of patients and was associated with soft pancreatic parenchyma and small wirsung duct. The reduced rate of PG bleeding observed with wrapping of the invaginated pancreatic stump warrants further evaluation in a prospective randomized study.