In process industries, the ignition of premixed combustible gases and oxidant is a major source of fires and explosions. To prevent such accidents, the knowledge of the auto-ignition temperature is of primary importance. Unfortunately, information on multicomponent fuels at high pressure is scarce. This requires a large experimental effort to identify safe operating conditions in the whole range of pressure and mixture composition of interest. This effort could be rationalized and minimized if a reliable modeling procedure to predict auto-ignition temperature values were available. In this work, the reliability of a procedure based on the use of detailed kinetic models together with easily accessible standard computational tools has been investigated using the urea production process (which involves mixtures of ammonia, hydrogen, methane, and air at high pressure and temperature) as an example. It has been found that the differences between model predictions and both experimental data measured in a laboratory-scale apparatus and values scaled up to real plant conditions never exceed 10%, thus confirming the reliability of the proposed procedure for auto-ignition temperature estimation.