Using a high-resolution hydrologic model, a land surface microwave emission model (LSMEM), and an explicit simulation of the orbital and scanning characteristics for the advanced microwave sensing radiometer (AMSR-E), an observing system simulation experiment (OSSE) is carried out to assess the impact of land surface heterogeneity on large-scale retrieval and validation of soil moisture products over the U.S. Southern Great Plains using the 6.925 GHz channel on the AMSR-E sensor. Land surface heterogeneity impacts soil moisture products through the presence of nonlinearities in processes represented by the LSMEM, as well as the fundamental inconsistency in spatial scale between gridded soil moisture imagery derived from in situ point-scale sampling, numerical modeling, and microwave remote sensing sources. Results within the 575 000 km(2) Red-Arkansas River basin show that, for surfaces with vegetation water contents below 0.75 kg/m(2), these two scale effects induce root mean squared errors (RMSEs) of 1.7% volumetric (0.017 cm(water)(3)/cm(soil)(3)) into daily 60 km AMSR-E soil moisture products and RMS differences of 3.0% (0.030 cm(water)(3)/cm(soil)(3)) into 60 km comparisons of AMSR-E soil moisture products and in situ field-scale measurements of soil moisture sampled on a fixed 25-km grid.