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High-fidelity, predictive fluid flow simulations of the interactions between the rising thermal plumes from forced air warming blower and the ultra-clean ventilation air in an operating room (OR) are conducted to explore whether this complex flow can impact the dispersion of squames to the surgical site. A large-eddy simulation, accurately capturing the spatiotemporal evolution of the flow in 3 dimensions together with the trajectories of squames, is performed for a realistic OR consisting of an operating table (OT), side tables, surgical lamps, medical staff, and a patient. Two cases are studied with blower-off and blower-on together with Lagrangian trajectories of 3 million squames initially placed on the floor surrounding the OT. The large-eddy simulation results show that with the blower-off, squames are quickly transported by the ventilation air away from the table and towards the exit grilles. In contrast, with the hot air blower turned on, the ventilation airflow above and below the OT is disrupted significantly. The rising thermal plumes from the hot air blower drag the squames above the OT and the side tables and then they are advected downwards toward the surgical site by the ventilation air from the ceiling. Temporal history of the number of squames reaching 4 imaginary boxes surrounding the side tables, the OT, and the patient's knee shows that several particles reach these boxes for the blower-on case., (© 2018 The Authors International Journal for Numerical Methods in Biomedical Engineering Published by John Wiley & Sons Ltd.)