Background: The primary goal of wound management is to achieve a functional closure with minimal scarring. One of the ways of wound management is to prescribe prophylactic antibiotics. This study compared single-dose intravenous (IV) prophylactic antibiotic with the common five-day treatment in simple traumatic and contaminated wounds.Methods: All patients with simple traumatic and contaminated wounds that were sutured and determined to have indications for prophylactic antibiotic therapy by a physician at emergency wards of Shohadaye Haftom-e-Tir and Rasoul-Akram Hospitals during working shifts of researchers were divided into two groups. The first group received a single-dose of IV cefazolin and the second group was treated with oral cephalexin for five days. Infection symptoms such as erythema, pus secretion and swelling were described to the patients. Patients were suggested to inform the researchers whenever they saw the symptoms before the exact date of suture removal.Findings: In this research, 150 patients were studied in two groups of 75. The first group received a single-dose IV antibiotic while the second received five days of antibiotic. Infection was observed in 6 (8%) and 7 (9.33%) patients in the first and second group, respectively. However, the two groups were not significantly different in terms of infection rate. Conclusion: The period of prophylactic antibiotic therapy does not seem to make significant differences in treatment of wounds. Therefore, based on the findings of previous studies, as well as ours, it can be concluded that using a single-dose IV prophylactic antibiotic might be preferable because it is more acceptable by patients and has fewer side effects.