Two prospective, randomized trials of the efficacy of antibiotic regimens after penetrating abdominal trauma demonstrated that a combination of clindamycin and tobramycin was superior to cefamandole or cefoxitin in preventing postinjury wound infection but that no difference could be demonstrated between combination therapy (clindamycin plus tobramycin) and moxalactam. Infection was more likely to occur after a gunshot wound or with a high injury severity score and occurred after the 10th postinjury day only in those patients who received cefamandole or cefoxitin. There was a higher incidence of culture of B. fragilis in the latter groups as well as infections due to resistant organisms. Short-term antibiotic therapy for 72 hours with either tobramycin plus clindamycin or moxalactam appears adequate for the majority of patients after gunshot or knife wounds. The costs of these regimens to the patient were similar in our hospital. The most important single factor, however, in maintaining low infection rates after penetrating injury to the abdominal cavity is appropriate and timely surgical management.