Background: Surgical site infections (SSIs) are known to be the third most common type of nosocomial (hospital acquired) infections and represent about 17% of their total incidence. The perioperative antibiotic prophylaxis (PAP) is an effective method for the prevention of surgical site infections (SSIs) because the vast majority of SSIs are caused by endogenous translocation of the patient's own microbiota. The use of perioperative antibiotic prophylaxis results in reduction of the total number of postoperative infections. In cardiothoracic surgery, the surgical site infections incidence is about 0.4-4%. Despite the marked advances in modern cardiothoracic surgical techniques and the use of pre-operative antibiotic prophylaxis, and careful wound treatment, surgical-site infections (SSIs) remain a dangerous and sometimes a lethal post-operative complication of cardiothoracic surgery operations. Aim of the study: This study aimed to compare and evaluate the difference between the outcome of the patients who didn't receive pre-operative antibiotic prophylaxis prior to elective adult conventional cardiothoracic surgery (Group A) with those patients who received pre-operative antibiotic prophylaxis (Group B) regarding the occurrence of post-operative wound infection, wound complications, patient's outcome, length of hospital stay and other post-operative complications. Patients and methods: This study was a single-center retrospective observational and comparative study, conducted on 500 adult patients scheduled for elective conventional cardiothoracic surgery operations at the Cardiothoracic Surgery Department, Tanta University Hospitals through the period from January 2018 to January 2023. The studied patients were divided into two groups according to their peri-operative management: (Group A): 250 patients who didn't receive pre-operative antibiotic prophylaxis and (Group B): 250 patients who received pre-operative antibiotic prophylaxis. Results: The mean ICU duration was 3.05 ± 2.18 days and the mean duration of the cardiothoracic operation was 208.03 ± 55.37 minutes. Among the studied patients there were 26 patients (5.2%) who had transient psychotic syndrome and 2 patients (0.4%) who had peri-operative myocardial infarction. There were 15 patients (3%) who died. There was a statistically significant correlation between the occurrence of postoperative infection and the incidence of post-operative patients' mortality. Conclusions: The use of perioperative antibiotic prophylaxis in cardiothoracic surgical patients was associated with significant reduction of postoperative wound infection. Most common cause in SSI after cardio-thoracic surgery was deep sternal wound infection. There was a significant corelation between SSI and post-operative mortality incidence in the patients undergoing elective cardio-thoracic surgery.