Surgical site infection (SSI) is a common complication of surgery and a major cause of morbidity, mortality and health care costs. Several patient and perioperative care related factors play a role in SSI, which above all is the result of a complex process. Timing of antibiotic prophylaxis (AP) is a process indicator that has been described extensively. However, the optimal timing remains controversial. A large SSI reduction was initially shown for administration of AP within two hours before incision. Later the optimal timing seemed to be 30-60 minutes or the final 30 minutes before incision. Recently, it has been shown that there is no significant association between timing and SSI. This controversy is reflected in several guidelines with dissimilar advice. If there is no optimal AP timing, it should not be a process indicator. Other SSI risk factors that are presently not the focus of attention may be more important process indicators.