Objectives: The current study aimed to compare the efficacy of the two different prophylactic antibiotic regimens (2-days vs. 7-days) in preventing surgical site infection in coronary artery bypass grafting (CABG). Methods: Patients undergoing CABG were included in this randomized, double-blind, placebo-controlled trial. From 2016 to 2017, 370 cases were allocated to one of two groups. The groups received prophylactic antibiotic therapy for either 2-days or 7-days. All CABG patients were followed for days for surgical site infections. Two of the patients died after surgery, and 3 patients did not show up during the three-month follow-up evaluation and thus did not meet the study criteria. Results: Of the remaining 365 patients who participated in the full study, 198 (54.2%) were male, and 167 (45.7%) were female patients. The mean age of these cases was 58.64± 11.4. Of the 365 study participants who received prophylactic antibiotics prior to surgery, 16 patients developed surgical site infections (legs and sternum). Among these 16 patients, nine cases belong to the 7-days prophylactic antibiotic therapy group (2.4%), and seven cases belong to the 2-day prophylactic antibiotic therapy group (1.9%) (P=0.771). Conclusion: Comparison of two 2-day and 7-day prophylactic antibiotic regimens showed no significant difference in the incidence of post-surgical infection in the two groups.