The number of long‐term survivors of pancreatectomy for cancer is increasing. This study was conducted in patients with periampullary cancer to elucidate the serial change in the pancreatic endocrine functions before and after resection of the head of the pancreas. The pancreatic A and B cell functions were determined by the responses of plasma glucagon and insulin to arginine infusion. For serial comparison, the maximum response and integrated increment of plasma glucagon and insulin were calculated in each patient. There were no significant differences in these parameters between the patients (n=36) before the operation and normal controls (n=18). Early after pancreatoduodenectomy (mean, 6.4 weeks), each parameter was significantly less than its corresponding preoperative value and also less than the value in the normal controls. In the long‐term survivors (mean, 20.1 months after the surgery; n=12) among these 36 patients, these parameters showed no significant changes compared with the early postoperative values and were still significantly less than both the preoperative values and the normal control values. We, thus, conclude that pancreatic A and B cell functions are preserved long‐term after pancreatoduodenectomy in patients with periampullary cancer.