The drill-and-blast method is widely used for the excavation of hard rock tunnels. Toxic gases such as carbon monoxide and nitrogen oxides are released immediately after blasting by the detonation of explosives. To provide a safe working environment, the concentration of noxious gases must be reduced below the threshold limit value according to health and safety regulations. In this paper, one-dimensional mathematical models and three-dimensional CFD numerical simulations were conducted to analyze the concentration, propagation and dilution of the blasting fumes under different operating conditions. Forced, exhaust and mixed ventilation modes were compared to determine the safe re-entry times after blasting in a 200 m-long tunnel excavated using the top-heading-and-benching method. Based on the numerical simulations, carbon monoxide was the most critical gas, as it required a longer ventilation time to reduce its concentration below the threshold limit value. The safe re-entry time reached 480 s under the typical forced ventilation mode, but was reduced to 155 s when a mixed ventilation system was used after blasting, reducing the operating costs. The reduction of the re-entry time represents a significant improvement in the excavation cycle. In addition, the results obtained show that 1D models can be used to preliminary analyze the migration of toxic gases. However, to reliably determine the safe re-entry times, 3D numerical models should be developed. Finally, to verify the accuracy of the CFD results, field measurements were carried out in a railway tunnel using gas sensors. In general, good agreements were obtained between the 3D numerical simulations and the measured values.