Symptomatic hyperinsulinemic hypoglycemia and pancreatic nesidioblastosis have recently been described in a small series of patients after gastric bypass surgery for morbid obesity. In the limited published reports of patients with this condition, hyperinsulinism and nesidioblastosis have been managed with distal or subtotal pancreatectomy, with the extent of resection guided by calcium angiography. However, nesidioblastosis may involve the pancreas diffusely, and limited pancreatic resections may predispose patients to further hypoglycemic episodes. We have treated two patients with refractory hyperinsulinism and symptomatic hypoglycemia after successful gastric bypass surgery. One patient underwent an approximately 80% pancreatectomy with good results but subsequently experienced recurrent drop attacks and fainting from hyperinsulinism; a completion pancreatectomy via a pancreaticoduodenectomy was then required. A second patient had profound hyperinsulinemic hypoglycemia and was treated successfully with a subtotal (95%) pancreatectomy. Our experience, the third published report of post-gastric bypass nesidioblastosis, suggests that the risk of recurrent symptomatic hyperinsulinism after limited pancreatectomy is significant and relative euglycemia may be achieved with subtotal or total pancreatectomy.