In using short-term antibiotic prophylaxis in clean orthopedic procedures we can avoid side effects and also it is more cost-effective. Background: Antibiotic therapy prevents postoperative infections after orthopedic procedures, but the method and prescribed dose of this therapy are debated. Short-term prophylaxis and long-term prophylaxis are 2 accepted methods after orthopedic procedures. Objectives: In this prospective observational study, we compared the results of shortterm and long-term prophylaxis after elective orthopedic procedures at 2 hospitals of Jundishapur University of Medical Sciences. Patients and Methods: We divided patients who underwent uneventful orthopedic operations into 2 groups, administered short-and long-term prophylactic antibiotic therapy, respectively, and observed the patients for signs and symptoms of superficial and deep infections. We compared and analyzed the results with SPSS, considering P values of less than 0.001 to indicate a significant difference. Results: There was no significant difference regarding superficial and deep infections between short-and long-term prophylaxis groups; thus, both methods can be used for prophylaxis after elective orthopedic surgeries, effecting equal rates of success. Conclusions: Short-term prophylaxis can be used for clean orthopedic procedures with equivalent results as long-term therapy.