Total pancreatectomy was rarely performed dreaded by its post-operative complications and mortality. With the improved post-operative management of the exocrine and endocrine deficiencies ensuing the removal of entire pancreas, the surgery is now being performed more frequently for various indications. Here we describe the total pancreatectomy for a patient with multifocal pancreatic ductal adenocarcinoma and the post-operative management of the patient. All patients become diabetic after total pancreatectomy and the control of blood sugar is really challenging due to extreme fluctuations in the levels. The exocrine deficiency is treated with pancreatic enzyme supplements; however, steatorrhoea, diarrhoea, weight loss, vitamin deficiencies, osteoporosis and osteopenia are still present even with effective management. Total pancreatectomy can still be performed safely with good post-operative outcomes in selected patients with specific indications.