A microkinetic analysis of the preferential oxidation of CO in H-2 over Ir-Fe/SiO2 catalyst is reported. Based on the results of in situ diffuse reflectance infrared spectroscopy, microcalorimetry, Mossbauer spectroscopy, and steady-state kinetic experiments in a microreactor, a microkinetic model is proposed that predicts the experimental results well. The model suggests that the reaction between adsorbed H and O for the formation of OH is rate-limiting for the PROX reaction, whereas the surface reaction between adsorbed CO and O is rate-determining for CO oxidation. In addition, the model predicts that the oxidation of adsorbed CO by surface OH is the dominant pathway for the PROX reaction. The surface coverages of different intermediates are also predicted by the model. According to this model, we can conclude that the presence of H-2 increases the surface concentration of OH and, hence, lowers the activation energy and increases the rate of the PROX reaction.