Introduction: Typhoid fever is an acute systemic infectious disease caused by Salmonella typhi bacteria. The disease is a health problem that occurs in many developing countries. Antibiotic is a routine habit for treating infectious diseases due to bacteria. The selection and use of appropriate and rational antibiotic therapy can determine a success in treatment to avoid bacterial resistance and minimize drug side effects. Objective: To determine the rationality of antibiotic use in adult patients with the diagnosis of typhoid fever in PKU Muhammadiyah Gamping Hospital. Method: This study is a non-experimental study with descriptive observational research design and retrospective data collection. The sample of this study is inpatients diagnosed with typhoid fever and recorded in PKU Muhammadiyah Gamping Hospital Medical Record Installation period January 2016 - December 2017 included in the inclusion criteria. Results: The data taken came from 75 medical records. The single most widely used antibiotic was levofloxacin in 27 cases (36%) and the most frequent antibiotic replacement was ceftriaxone in 18 cases (24%). The appropriate use of antibiotics in 75 patients (100%), appropriate types in 75 patients (100%), appropriate duration of administration in 64 patients (85.33%), appropriate dose in 73 patients (97.33%), appropriate intervals in 73 patients (97.33%) and appropriate route of administration in 75 patients (100%). Qualitative evaluation of antibiotic prescribing with the Gyssens method found 25 prescriptions (33.33%) in the IVA category (there are other more effective antibiotics), 1 prescription (1.33%) in the IIIA category (too long administration), 1 prescription (1.33%) in IIIB category (giving too short), 1 prescription (1.33%) in IIA category (incorrect dose), and 47 prescriptions (62.67%) in 0 category (accuracy of prescribing).