INTRODUCTION: Cystic fibrosis (CF) is an inherited disorder that presents in childhood as a multisystem disease. Pulmonary failure and pancreatic insufficiency, including CF-related diabetes (CFRD) and exocrine insufficiency, are significant causes of morbidity and mortality in these patients. In this report we have reviewed our experience with a simultaneous lung and pancreas transplantation in a patient with CF. METHODS: The recipient was a 25-year-old man with CF complicated by bronchiectasis with recurrent episodes of pneumonia, pancreatic exocrine insufficiency, and CFRD. He had normal hepatic and renal function. SURGICAL TECHNIQUE: The lung and pancreas allografts were procured from a single cadaveric donor. The double lung transplantation was performed through separate thoracic incisions. The pancreas transplantation was performed through a midline incision with systemic venous drainage and proximal enteric exocrine drainage. RESULTS: The recipient recovered well from his transplantation with early extubation. The pancreas allograft functioned well with normal blood glucose independent of insulin. As a result of the enteric drainage of the pancreas allograft, the patient no longer required supplemental pancreatic enzymes. His postoperative course was complicated by distal intestinal obstruction, a complex wound infection, and reversible leukoencephalopathy. At 1-year posttransplantation he remains free of supplemental oxygen, insulin, and pancreatic enzyme replacement. CONCLUSION: Simultaneous lung and pancreas transplantation in a patient with CF was performed safely, providing the advantages of normalization of glucose and improved nutrition for a patient requiring lung transplantation.