Catalytic partial oxidation (CPO) is an important technology for producing hydrogen from methane. A two-membrane CPO reactor, which has both an O-2 membrane and a H-2 membrane, integrates various processing steps in a single reactor. It has many advantages, compared to a conventional CPO reactor or a single-membrane reactor. The intent of this work is to simulate and investigate the thermodynamic efficiency of the process with a two-membrane reactor to produce pure hydrogen for application to fuel cells. The simulation of the two-membrane CPO reactor is based on the kinetics of the reactions and the mechanisms of membrane permeation. Other units of the process, which include a polymer electrolyte membrane (PEM) fuel cell, a catalytic burner, compressors, and heat exchangers, have also been simulated. On the basis of simulation results, the thermodynamic analysis of the process has been performed. The effect of the inlet temperature of air, the inlet pressure, the flowing mode of the sweeping gas, and the fraction of H-2 recovered on the production rate of useful products (H-2 and CO) of the two-membrane CPO reactor, and on the thermodynamic efficiency of the integrated process, have been discussed.