Fire is a major hazard in hospitals, often caused by flammable liquids and medical gases, and can lead to significant losses due to limited patient mobility. This study simulated the effectiveness of portable and ceiling exhaust systems in reducing smoke, heat, and toxic gases in a hospital Neonatal Intensive Care Unit (NICU) using Computational Fluid Dynamics (CFD).The study began by converting a 2D sketch of the NICU into a 3D model using SketchUp, which was then imported into PyroSim software. Properties of objects and fire scenarios were set in PyroSim, and simulation results for temperature, visibility, and toxic gases (CO, CO2, O2) were generated as 3D cross-sectional views and profiles.In the simulation, the ceiling exhaust contained smoke within the fire room, preserving visibility in other areas, while the portable exhaust spread smoke to corridors, reducing visibility to zero. The ceiling exhaust maintained temperatures between 60–70°C, while the portable exhaust exceeded 80°C. CO concentrations peaked at 700 ppm without exhaust, dropped to 400 ppm with portable exhaust, and 300 ppm with ceiling exhaust. Oxygen levels fell to 18% with either exhaust, but remained at 20% with ceiling exhaust. The ceiling exhaust also reduced CO2 in exit rooms from 18,000 ppm to below 12,000 ppm, while portable exhaust reduced it by only 2,000 ppm. These findings can guide hospital designers and firefighting teams in selecting optimal fire control equipment, enhancing building safety and firefighting strategies.