The use of antibiotic prophylaxis was prospectively evaluated in 1,021 surgical patients from 27 hospitals in metropolitan Minnesota. The majority of patients had undergone general surgical (23%), obstetric and gynecologic (13%), orthopedic (26%), and urologic (12%) procedures. One half of the courses of antibiotic prophylaxis were given to patients undergoing clean (class 1) surgery. Antibiotics were first administered in the four hours preceding the start of surgery in only 41% of the patients. The mean duration of prophylaxis was 3.4 days. About one third of the patients received prophylaxis for more than 72 hours; this group accounted for 65% of patient-days of antibiotic administration. More than one half of the patients received a cephalosporin. Analysis of patient charges suggests that 18% to 50% of the cost of perioperative antibiotic prophylaxis might be saved by limiting the duration of drug administration.