Objectives:The goal of this study was to evaluate the impact on a protocol change of surgical antimicrobial prophylaxis in cardiac surgery comparing the new in hospital prophylactic agent cefazolin versus the former standard antibiotic cefuroxime, initiated by the antimicrobial stewardship team. Methods: This retrospective observational study was performed in a tertiary care hospital in collaboration with the department of cardiothoracic surgery and the antimicrobial stewardship team following a new recommendation of the surgical antimicrobial prophylaxis and included 1029 patients who underwent cardiac surgery. Two patient groups including 582 patients receiving Cefuroxime and 447 patients receiving Cefazolin respectively were compared without altering any other preventative perioperative measures. Adherence, overall infection rates, leg wound infections and deep sternal wound infections were compiled and analysed as well as a broad profile of preoperative, intraoperative and postoperative patient data. Results:A complete adherence on the change of the agent was achieved.Overall surgical site infections occurred in 37 (6.6%) of the cases, with 20 (3,4%) SSI in cefuroxime patients and 17 (3,8%) in cefazolin patients (p-value=0,754). No statistically significant differences could be found in any of the primary and secondary endpoints including DSWI (2,1% for cefuroxime, 1,3% for cefazolin), vein harvesting site infections (1,2% for cefuroxime, 2,2% for cefazolin) as well as urinary tract infections, pneumonia, sepsis and overall mortality of all causes. Conclusions:These results demonstrate that compliance to antimicrobial stewardship standards is not associated with more surgical site infections.