Physicians working in casualty and outpatient departments where adverse conditions prevail often prescribe antibiotic prophylaxis routinely at the time of suture repair of simple wounds. To evaluate this practice, we performed a randomized, controlled study of parenteral chemoprophylaxis of simple wounds undergoing suture repair. Uncomplicated wounds were randomized to either treatment with a combination of benzathine penicillin (2.4 million units) and procaine penicillin (2.0 million units) intramuscularly, or a control group. At the time of suture removal, seven days later, all wounds were reviewed for signs of infection. Of 320 patients enrolled in the study, 173 (54.1%) returned for review. Among treated wounds, 75 of 81 (92.6%) were healing, compared to 79 of 92 (85.9%) controls (p = 0.24). A significantly higher rate of healing was observed when wounds repaired nine or more hours after injury and involving the arms, legs, or trunk were treated (22 of 23, 95.7%) compared to those in whom prophylaxis was omitted (20 of 30, 66.7%) (p = 0.03). Wounds involving the head, and wounds repaired within nine hours after injury had a high rate of healing (greater than 90%), whether prophylaxed or not. Based on a 30% higher healing rate for the patients who benefited from treatment (arm, leg, trunk wounds repaired after nine or more hours), the drug cost of implementing prophylaxis for this group alone was more than five times that of an expectant, non-prophylactic strategy. These results serve to remind practitioners of the possibility that a clinically effective mode of therapy may not necessarily be cost-effective in the delivery of health care.