Improved surgical and anesthetic techniques and postoperative care have not significantly changed wound infection rates over the last 30 years. Many risk factors, related both to the host and to the surgical practice, have been identified in different studies. Control of nosocomial infections has become more challenging recently, due to a widespread bacterial resistance to antibiotics and to more frequent surgical indications in elderly patients at increased risk. A change in the microbiology of postoperative infections has also been noticed, characterized by a greater incidence of infections caused by methicillin-resistant Staphylococcus aureus, by polymicrobic flora and by fungi. This paper reviews the most important risk factors encountered in general surgery, that we observed during a 6-year prospective study of wound infection carried out in our Department of Surgery at the University of Insubria in Varese. Furthermore, the epidemiologic data on wound infections recorded in 4,002 patients undergoing general surgical procedures (mostly gastrointestinal operations), are presented and discussed.