Controlling respiratory contaminants in airborne infection isolation rooms (AIIRs) is essential to minimize transmission risk and protect healthcare workers. While background ventilation is a widely used and effective engineering strategy for infection control, source-oriented local ventilation offers a more targeted alternative. This study explores a ceiling-mounted local exhaust concept for AIIRs, designed to capture coughing particles in a practical and flexible way. We employed the Eulerian-Lagrangian framework to simulate transient airflow and particle dispersion in AIIRs. Four exhaust configurations were tested under different coughing behaviors. Our findings reveal that the capture efficiency of the above-chest exhaust drops from 97% to 7% with a change in coughing angle, while the ceiling-mounted exhaust maintains an efficiency of 20–40%. The ceiling-mounted solution exhibits higher capture stability and greater resilience across different conditions. Subsequent trajectory analysis of 16 variants identifies the influence of heat-source arrangement and ventilation flow direction on particle transport. A real-ward case study further indicates that the ceiling-mounted local exhaust system can suppress the initial concentration peak in the breathing zone, demonstrating short-term exposure reduction under a representative clinical layout. Overall, this work presents an adaptive, source-oriented ceiling-mounted local exhaust approach for effective short-term removal of coughing particles in AIIRs.