Clinical and laboratory experience has shown that prophylactic antibiotics may be effective in trauma when the period of contamination is brief, defined and predictable. Prevention of infections has been achieved in the treatment of penetrating abdominal wounds, open fractures, and early wounds that can be adequately debrided and closed. Prophylactic antibiotics do not prevent infection in wounds left open, in wounds that are incompletely debrided or treated very late, following tracheal intubation, after urinary tract catheterization, or after vascular cannulation. Continuing contamination is the primary reason for ineffectiveness in these situations, and the prolonged use of prophylactic antibiotics only serves to make the ensuing infections antibiotic-resistant. Prophylactic antibiotics should be administered for only a brief period of time, i.e., immediately preoperatively, intraoperatively, and for only a short while postoperatively. In studies of the effectiveness of prophylactic antibiotics in elective clean-contaminated or contaminated operations, only a single dose of antibiotics has been shown to be effective, and prolonged administration may actually increase the incidence of infection. On the other hand, such studies have not been reported in patients with trauma. Prophylactic topical antibiotics may be used either alone or as an adjunct to systemic antibiotics, but if used in conjunction with systemic antibiotics, the topical antibiotic should be of a different type to prevent potential toxicity.