Space reactors with fast neutron energy spectrums are preferred for their compactness and high fission power density, but require a high fissile inventory. The operation life estimates of these reactors are important to mission planning. This paper examines a number of fuel depletion and neutronics code packages for determining the operation lives of two space reactors with hard fast neutron energy spectra. These are: the lithium-cooled, Sectored, Compact Reactor (SCoRe-S11), and the submersion subcritical safe space (S^4) reactor, cooled with a He-Xe binary gas mixture (40 g/mol). This work investigated the code packages of Monteburns 2.0, MCNPX 2.6C and TRITON and validated their prediction with fuel depletion data for a PWR fuel bundle, with satisfactory results. The operation life predictions of the two space reactors using these code packages are compared with those calculated using a simplified method that couples MCNP5 to a burnup analysis model using the Simulink® platform. This method considers only the 10 most probable low-Z and high-Z elements of the fission yield peaks plus 149Sm, and neglects the depletion of fission products due to capture and radioactive decay. The simplified method requires significantly shorter running time and its predictions of the operation lives for the two space reactors are within 0.29-12.5% of those obtained using Monteburns 2.0 and MCNPX 2.6C code packages. This method, however, is not recommended for operation life predictions for space or commercial reactors with thermal neutron spectrums. © 2008 Elsevier Ltd. All rights reserved.