Postoperative infections are not consistently controlled by current practice measures. From a recent study of 12,384 patients, postoperative infection occurred in 22% of colorectal procedures and 25% of upper gastrointestinal procedures. Infections were associated with a higher death rate, longer hospitalization, and more intense post-discharge care. Control of infections for clean-contaminated procedures requires effective bowel cleansing when appropriate, meticulous surgical technique, and timely antimicrobial administration. Many patients undergoing clean-contaminated surgery do not receive properly timed antimicrobials. Although the comparative value of oral (neomycin and erythromycin) or parenteral antimicrobials for colon surgery remains an unresolved issue, the combination can be beneficial for many colorectal operations. Third generation cephalosporins are not consistently more effective than older agents such as cefoxitin and increase bacterial resistance. Improper antimicrobial timing is one of the most common problems with surgical prophylaxis and is fully under the control of the surgeon. To maximize benefits of antimicrobial prophylaxis, systems should be devised to assure timely administration.