When infectious epidemics occur, they can be perpetuated within health care settings, potentially resulting in severe health care workforce absenteeism, morbidity, mortality, and economic losses. The ventilation system configuration of an airborne infection isolation room is one factor that can play a role in protecting health care workers from infectious patient bioaerosols. Though commonly associated with airborne infectious diseases, the airborne infection isolation room design can also impact other transmission routes such as short-range airborne as well as fomite and contact transmission routes that are impacted by contagion concentration and recirculation. This article presents a computational fluid dynamics study on the influence of the ventilation configuration on the possible flow path of bioaerosol dispersal behavior in a mock airborne infection isolation room. At first, a mock airborne infection isolation room was modeled that has the room geometry and layout, ventilation parameters, and pressurization corresponding to that of a traditional ceiling-mounted ventilation arrangement observed in existing hospitals. An alternate ventilation configuration was then modeled to retain the linear supply diffuser in the original mock airborne infection isolation room but interchanging the square supply and exhaust locations to place the exhaust closer to the patient source and allow clean air from supply vents to flow in clean-to-dirty flow paths, originating in uncontaminated parts of the room prior to entering the contaminated patient’s air space. The modeled alternate airborne infection isolation room ventilation rate was 12 air changes per hour. Two human breathing models were used to simulate a source patient and a receiving health care worker. A patient cough cycle was introduced into the simulation, and the airborne infection dispersal was tracked in time using a multi-phase flow simulation approach. The results from the alternate configuration revealed that the cough aerosols were pulled by the exhaust vent without encountering the health care worker by 0.93 s after patient coughs and the particles were controlled as the aerosols’ flow path was uninterrupted by an air particle streamline from patient to the ceiling exhaust venting out cough aerosols. However, not all the aerosols were vented out of the room. The remaining cough aerosols entered the health care worker’s breathing zone by 0.98 s. This resulted in one of the critical stages in terms of the health care worker’s exposure to airborne virus and presented the opportunity for the health care worker to suffer adverse health effects from the inhalation of cough aerosols. Within 2 s, the cough aerosols reentered and recirculated within the patient and health care worker’s surroundings resulting in pockets of old contaminated air. By this time, coalescence losses decreased as the aerosol were no longer in very close proximity and their movement was primarily influenced by the airborne infection isolation room airflow patterns. In the patient and heal...