Background Hospital-acquired infections account for a substantial increase in morbidity and mortality. This prospective, single-center observational study was conducted to assess the incidence and analyze the risk factors of nosocomial infection after peripheral arterial bypass surgery. Methods The incidence of nosocomial infections was registered in all patients undergoing peripheral arterial bypass surgery from January 1996 until December 2004, and risk factors for the development of a nosocomial infection were analyzed. Results A total of 67 infections were diagnosed in association with 607 procedures, yielding an infection ratio of 10.0%. Surgical site infection was the most common (55.2%), followed by urinary tract infection (16.4%), pneumonia (14.9%) and bacteremia (10.4%). Staphylococcus aureus was the most commonly found isolate in surgical site infections (48.6%) and in bacteremia (42.9%). Age, the use of corticosteroids (p = 0.02), and critical ischemia with tissue loss (p = 0.009) could be identified as risk factors for the development of a nosocomial infection.