Introduction: Pancreatic leak or fistula is the most frequent complication after left pancreatectomy. We performed a single-blinded, parallel-group, randomized controlled trial comparing stapled left pancreatectomy with stapled left pancreatectomy using mesh reinforcement of the staple line with either Seamguard or Peristrips Dry. Methods: All patients undergoing left pancreatectomy at a large tertiary hospital were eligible for participation. Patients were randomized to either mesh reinforcement or no-mesh reinforcement intraoperatively after being determined a candidate for resection. Patients were blinded to the result of their randomization for 6 weeks. Primary outcome measure was clinically significant leak as defined by the ISGPF (International Study Group on Pancreatic Fistula) pancreatic leak grading system. Results: One hundred patients were randomized to either mesh (54) or no-mesh (46) reinforcement of their pancreatic transection. There was 1 death in each group. ISGPF grade B and C leaks were seen in 1.9% (1/53) of patients undergoing resection with mesh reinforcement and 20% (11/45) of patients without mesh reinforcement (P = .0007). Conclusions: Mesh reinforcement of pancreatic transection line significantly reduces the incidence of significant pancreatic fistula in patients undergoing left pancreatectomy.