In this research, ORIGEN cross section libraries for reactor-grade mixed oxide (MOX) fuel assembly designs have been developed to provide fast and accurate depletion calculations to predict nuclide inventories, radiation sources and thermal decay heat information needed in safety evaluations and safeguards verification measurements of spent nuclear fuel. These ORIGEN libraries are generated using two-dimensional lattice physics assembly models that include enrichment zoning and cross section data based on ENDF/B-VII.0 evaluations. Using the SCALE depletion sequence, burnup-dependent cross sections are created for selected commercial reactor assembly designs and a representative range of reactor operating conditions, fuel enrichments, and fuel burnup. The burnup dependent cross sections are then interpolated to provide problem-dependent cross sections for ORIGEN, avoiding the need for time-consuming lattice physics calculations. The ORIGEN libraries for MOX assembly designs are validated against destructive radiochemical assay measurements of MOX fuel from the MALIBU international experimental program. This program included measurements of MOX fuel from a 15 × 15 pressurized water reactor assembly and a 9 × 9 boiling water reactor assembly. The ORIGEN MOX libraries are also compared against detailed assembly calculations from the Phase IV-B numerical MOX fuel burnup credit benchmark coordinated by the Nuclear Energy Agency within themore » Organization for Economic Cooperation and Development. Finally, the nuclide compositions calculated by ORIGEN using the MOX libraries are shown to be in good agreement with other physics codes and with experimental data.