Background: SSI is a surgical site infections or organ / space that occurs within 30 days after surgery or within one year if there are implants. Source of bacteria on SSI can be derived from the patient, the doctor and the team, the environment, and also the instrumentation. Prevention of SSI should be done, because if not, it can be resulted in an increasingly duration of hospitalization, increased costs of treatment, the risk of disability and death, and can lead to patient’s claim. Irrational use of antibiotics can have a negative impact, one of them is the increase incidence of bacterial resistance to antibiotics. Therefore, the rational use of antibiotics is expected to have a positive impact which is to decreased morbidity, mortality, economic loss, and reduce the incidence of bacterial resistance to antibiotics. Methods: This research was a descripive study to determine the rationality of the use of antibiotics in patients SSI. Data were collected retrospectively from patient records. The research sample was all the medical records of SSI patient’s who received antibiotic therapy at RS PKU Muhammadiyah Yogyakarta during the period January to April 2015. Assessment of the rationality usage of antibiotics is done using Gyssens method. The analysis was done descriptively to the appropiateness of indication, the appropiateness of antibiotic choices, the appropiateness of duration of therapy, the appropiateness of dosage and frequencies, dan the appropiateness of route. Results: Based on the assessment by Gyssens method showed 89.86% for category VI (incomplete data), 31.88% for category V (there was no indication of usage), 99.18% for the category IVD (there were antibiotics which was more specific), 87.70% for the category IIIA (the usage of antibiotics was too long), 30.33% for the category IIA (inappropriate dosages), 30.33% for the category IIB (inappropriate frequencies), and 0 , 82% for categories of IIC (inappropriate routes), and 0% for the category 0 (rational antibiotic use). Conclusion: There were no cases of SSI in the period January to April 2015. The rationality usage of prophylactic antibiotics in surgery at RS PKU Muhammadiyah period January to April 2015 based of Gyssens methods were irrational.