Efficiency is the key parameter for the application of fuel cells in automotive applications. The efficiency of a hydrogen/oxygen polymer electrolyte fuel cell system is analyzed and compared to hydrogen/air systems. The analysis is performed for the tank to electric power chain. Furthermore, the additional energy required for using pure oxygen as a second fuel is analyzed and included in the calculation. The results show that if hydrogen is produced from primary fossil energy carriers, such as natural gas and pure oxygen needs to be obtained by a conventional process; the fuel to electric current efficiency is comparable for hydrogen/oxygen and hydrogen/air systems. However, if hydrogen and oxygen are produced by the splitting of water, i.e., by electrolysis or by a thermochemical process, the fuel to electric current efficiency for the hydrogen/oxygen system is clearly superior.