In this study the influence of cathodic and anodic pressures during polymer electrolyte membrane water electrolysis on the gas crossover is simulated and compared to in-situ measurements of the anodic hydrogen content at differential and balanced pressure operation. The efficiency losses due to the reduced Faraday efficiency caused by crossover, ohmic loss of the membrane and pressurized hydrogen and oxygen evolution are estimated. Therefore, the correlated dependencies on the current density, membrane thickness, anodic and cathodic pressures, membrane conductivity and permeabilities are quantified. In addition, pressurized electrolysis is compared to adiabatic and isothermal subsequent compression in focus of efficiency. The outcome of this study can be utilized as a powerful computational tool to optimize the membrane thickness with respect to the operating pressures. Copyright (C) 2013, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.