A large amount of surgical smoke in electrosurgery seriously deteriorates the clean environment of the operating room and can potentially harm medical staff and patients. Exploring the distribution and removal of indoor particulate matter and selecting efficient ventilation patterns are effective ways to control harmful smoke. Therefore, in this study, we combined simulations and full-scale experiments to quantitatively explore the high-concentration spatial regions of particles and compared three ventilation patterns: vertical laminar airflow (VLAF), horizontal laminar airflow (HLAF), and hybrid ventilation, wherein unidirectional airflow (UDAF) was applied to the operating table along with peripheral mixing (UDAF + mixing). We found that simple laminar flow ventilation was significantly affected by the equipment layout and air change rate (air changes per hour; ACH), and the smoke particles were distributed in large amounts in the operating area and could not be removed completely. Conversely, hybrid ventilation can work effectively, and the optimal ACH is approximately 60, which can remove nearly 72% of smoke particles. The airflow distribution in the operating room is also an important factor affecting the distribution and removal of smoke particles. Therefore, medical staff should avoid prolonged exposure to areas with high particle concentrations and particle removal paths.