The highest sensitivity, lowest dark current infrared focal plane arrays (IRFPAs) are produced using HgCdTe on CdZnTe substrates. As-received state-of-the-art CdZnTe 6 × 6 and 7 × 7.5 cm substrates were analyzed using Nomarski phase contrast microscopy, Auger electron spectroscopy, scanning electron microscopy/energy dispersive spectroscopy, and scanning profilometry. On all CdZnTe substrates tested, we observed as-received large area macro-defect contamination. Using a defect specification limit of 50 contiguous defective pixels, we identified non-compliant 1280 × 720 12-μm pitch focal plane arrays due to as-received substrate macro-defect contamination. Using the above specification, up to 20% IRFPA wafer yield loss is due to state-of-the-art as-received CdZnTe substrate macro-contamination.