The high prevalence rate of typhoid fever is one of the health problems in Indonesia. Antibiotic therapy is the only therapy that can be used to treat the main cause of typhoid fever. Antibiotics are a type of drug therapy that requires a lot of budgets to procure. This study aims to find out the most cost-effective type of antibiotic for treating typhoid fever. This research was conducted at Kartini Rangkasbitung Hospital using observational research methods with a cross-sectional approach. The data used uses secondary data conducted retrospectively. This research uses medical record data and cost data. This study was divided into three groups, namely ciprofloxacin tablets, intravenous ceftriaxone, levofloxacin tablets and intravenous levofloxacin. Based on the calculation results, the ACER value of ceftriaxone is IDR 2,955,250, the ACER value of IV levofloxacin is IDR 2,727,306, and the ACER value of levofloxacin tablets is IDR 3,047,337. The ICER value from the comparison between levofloxacin tablets and ceftriaxone is IDR 43,250. The most cost-effective antibiotic is the antibiotic levofloxacin in intravenous form.