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Impacts of the laminar airflow ventilation system design factors on contaminant removal and thermal comfort condition in an operating room have been investigated by means of Lagrangian-based particle transport using the non-Boussinesq modeling of the buoyancy effects. An operating room including staffs and a patient with realistic human geometries and two surgery lights are included in simulations. The laminar airflow system is placed on the ceiling with a surrounding fixed-height partial wall and the air barrier supply grills. Effects of density change in mixed convection flow regime are included by the non-Boussinesq modeling of the exact air density variation. The predicted mean vote, the age of air, the colony-forming units per cubic meter, the average temperature, the average velocity, the relative humidity, the density distribution, and the positions of particles are calculated to assess the indoor air ventilation quality. A total of 27 simulation cases have been considered to determine the impact of three main design factors including the laminar airflow system area, the supply air, and the air barrier velocities on the performance of the system. It is concluded that for the curtain velocity of 2 m/s, the thermal comfort reduces with increasing the laminar airflow velocity, but for the third staff, the results show that for small laminar airflow areas, the speed of the inlet port should be reduced and for the larger sizes, the inverse of this trend is recommended. Moreover, for all cases the humidity varies within the range of 55%–56%, which agrees well with the suggested standard humidity range between 50% and 60%. It is concluded that the cases of the laminar airflow velocity equal to 0.3 and 0.5 at the curtain velocity of 1 m/s are generally more appropriate than other cases due to less accommodation of particles near the entire body of the patient. [ABSTRACT FROM AUTHOR]