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The effects of heavy ion energy and nuclear interactions on the single-event upset (SEU) and single-event latchup (SEL) response of commercial and radiation-hardened CMOS ICs are explored. Above the threshold LET for direct ionization-induced upsets, little difference is observed in single-event upset and latchup cross sections measured using low versus high energy heavy ions. However, significant differences between low- and high-energy heavy ion test results are observed below the threshold LET for single-node direct ionization-induced upsets. The data suggest that secondary particles produced by nuclear interactions play a role in determining the SEU and SEL hardness of integrated circuits, especially at low LET. The role of nuclear interactions and implications for radiation hardness assurance and rate prediction are discussed.