Poststernotomy mediastinitis is a challenge in each cardiac surgery, specially CABG, with severe effect on the patient and increased costs for health authorities.We aim at evaluation of the efficacy of local vancomycin application in prevention of poststernotomy infection and mediastinitis in high risk CABG patients, who have one or more risk factor for SWI. Methods: Our study was performed from 2019 to the end of 2020. It included 80 high risk CABG patients for SWI divided into two equal groups; vancomycin and control groups. The vancomycin group had local sternal vancomycin paste application prior to reinforced sternal closure prepared by mixing 2.5 grams of powdered vancomycin with 3 ml normal saline and stirred until a paste was formed. The control group had reinforced closure technique without vancomycin paste application. All cases were followed up for symptoms and signs of SWI. Results: Results shows a significantly increased prevalence of poststernotomy superficial wound infection among patients of control group (P-value=0.02). Purulent discharge was detected in 8 cases of control group versus no cases in vancomycin group (20% , 0.0% respectively), serous discharge (1 case in control group (2.5%) versus 2 cases in vancomycin group(5%)) and early partial sternal rocking (1 case in the control group (2.5%) versus 2 cases in the vancomycin group (5%)). 1 case had late sternal dehiscence with deep mediastinitis in the control group (2.5%) versus no cases of deep mediastinitis in the vancomycin group (0.0%). Conclusion: Application of local sternal vancomycin significantly reduces poststernotomy wound superficial wound infection and possibly prevents deep mediastinitis.