The objective of this study was to assess the impact of an intervention to modify antitetanus prophylaxis of open wounds. This prospective, before-and-after study was conducted in an emergency department of a large metropolitan hospital. Consecutive patients with open wounds were managed according to the World Health Organization (WHO) guidelines before an intervention, then according to new guidelines afterwards. Locally developed guidelines were introduced and backed up by a teaching program, with emphasis on reducing unwarranted human tetanus immunoglobulins and costs. Serum tetanus antitoxins level was measured in postintervention patients mainly to verify the soundness of the intervention, eventually to complete patients' protection during follow-up, and to derive more reliable recommendations for the future. Main outcome measures included the number of treatments conforming to each set of guidelines, the rate of tetanus immunoglobulin prescriptions, and the cost of each strategy. Two groups of 389 and 459 patients were included. Treatment conforming to guidelines increased from 60% to 79%, under-treatment decreased from 31% to 19%, and overtreatment decreased from 9% to 2% (P < 0.001). Tetanus immunoglobulin prescriptions decreased from 23% to 1% (P < 0.001). On the basis of antitoxins level, 60% of 367 postintervention patients were correctly treated, 29% were overtreated, and 11% were undertreated. Nevertheless, with the WHO guidelines, only 49% would have been correctly treated, 39% would have been overtreated (29% with immunoglobulins), and 12% would have been undertreated (P < 0.001). Costs decreased from $32 to $24 per patient. New guidelines resulted in improved tetanus prophylaxis at reduced costs in an emergency department. Because they rely on immunization history, however, guidelines currently in use are misleading. More reliable recommendations, including a test for tetanus antibody status in some cases, are needed.