For combined kidney and pancreas transplant recipients infectious complications remain a major source of morbidity. With as many antibiotic protocols as transplant centers, the exact type and duration for prophylactic wound antibiotics remains undefined. A retrospective review of our series of 40 combined kidney and pancreas transplants was performed using a single 1 g dose of cefazolin preoperatively along with cefazolin bladder and intra-abdominal irrigation. Two patients developed superficial wound infections for a rate of 5% (2/37). The deep wound infection rate was 11% (4/37), and all followed either a bladder anastomotic leak or the initial development of transplant pancreatitis. Our overall rate of 16% is very comparable with other series of combined kidney and pancreas transplant recipients. To help eliminate the potential development of superinfections and resistant organisms, a single dose of antibiotics appears to be as effective for wound prophylaxis in these patients when compared to multiple-antibiotic and multiple-day regiments. A randomized prospective study of prophylactic antibiotics in combined kidney and pancreas transplants is needed.