Background: The use of irrationale antibiotics is very often, including in case of a clean operation. It could result an increasing of cost and risk of antibiotic resistancy. Methodology: This study was conducted an experimental study using the One-Shot Case Study Quasy Experimentale. Antibiotics studied were Cefotaxime, Ceftriaxone and Cefazoline and applied to the operation of an inguinal hernia, goiter, soft tissue tumors and benign breast tumor. Drug prices are nominal prices pharmacy (HNA). Results: The study sample as many as 136 patients and controls with the same amount. Surgical Site Infection (SSI) of the sample is 2 cases and the control is 3 cases. The control variables of comorbid factors are held constant. Ceftriaxone is the most effective and efficient antibiotic based on the analysis of ACER and ICER when used rationally. Efficiency result could be used for supporting hospital development, handrub and research.