The risk of infection is present in any operating procedure. Every year, more than 300 million surgical operations occur globally. Around 38 percent of them face complications caused by surgical site infection (SSI). This infection can increase mortality rate and treatment costs while prolonging the hospitalization time of patients. Bacteria-carrying particles (BCP) are the main cause of surgical site infection. Such contaminated particles can enter the open wound region of the patient during surgery and cause infection. The particle source could be from uncovered skin of the personnel around the surgical table or other micro particle dusts floating around the operating room within the air. Particles can also be transferred through the use of surgical instruments that are located on the side table, after micro partciles were deposited on the instruments. Therefore, it is critical to improve operating rooms (OR) ventilation systems to reduce BCPs. The 3 typical ventilation systems within operating rooms are (1) a single large laminar diffuser at above the surgery table, (2) an array of multiple laminar diffusers or (3) an air curtain system around the surgery table. All these systems tend to decrease the particle concentration near the surgical site by either dilution or extraction of the infected particle from the site. In this study, Computational Fluid Dynamics (CFD) is used to compare the effectiveness of each of these systems within a mid-size operating room with staff and surgical devices around the patient. Contaminated particles are generated and tracked from both inside and outside the sterile zone. This study introduces a novel methodology to demonstrate ventilation optimization using CFD. Results show that ventilation systems that provide better laminar downward flow direction at above the surgery table can provide better protection for the sterile zone.