Background: Necrotizing pancreatitis may lead to loss of integrity of the pancreatic duct, resulting in leakage of pancreatic fluid. Pancreatic duct disruption or disconnection is associated with a prolonged disease course and particular complications. Since a standard treatment for this condition is currently lacking, we performed a systematic review of the literature to compare outcomes of various treatment strategies. Methods: A systematic review was performed according to the PRISMA guidelines in the PubMed, EMBASE and Cochrane databases. Included were articles considering the treatment of patients with disrupted or disconnected pancreatic duct resulting from acute necrotizing pancreatitis. Results: Overall, 21 observational cohort studies were included comprising a total of 583 relevant patients. The most frequently used treatment strategies included endoscopic transpapillary drainage, endoscopic transluminal drainage, surgical drainage or resection, or combined procedures. Pooled analysis showed success rates of 81% (95%-CI: 60–92%) for transpapillary and 92% (95%-CI: 77–98%) for transluminal drainage, 80% (95%-CI: 67–89%) for distal pancreatectomy and 84% (95%-CI: 73–91%) for cyst-jejunostomy. Success rates did not differ between surgical procedures (cyst-jejunostomy and distal pancreatectomy (risk ratio = 1.06, p = .26)) but distal pancreatectomy was associated with a higher incidence of endocrine pancreatic insufficiency (risk ratio = 3.06, p = .01). The success rate of conservative treatment is unknown. Discussion: Different treatment strategies for pancreatic duct disruption and duct disconnection after necrotizing pancreatitis show high success rates but various sources of bias in the available studies are likely. High-quality prospective, studies, including unselected patients, are needed to establish the most effective treatment in specific subgroups of patients, including timing of treatment and long-term follow-up.