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Clock-domain crossing (CDC) faults are a serious concern for high-speed, multi-core integrated circuits. Even when robust design methods based on synchronizers and design verification techniques are used, process variations can introduce subtle timing problems that affect data transfer across clock-domain boundaries for fabricated chips. We present a test generation technique that leverages commercial ATPG tools, but introduces additional constraints, to detect CDC faults. We also present HSpice simulation data using a 45 nm technology to quantify the occurrence of CDC faults at clock-domain boundaries. Results are presented for synthesized IWLS05 benchmarks that include multiple clock domains. The results highlight the ineffectiveness of commercial transition-delay fault ATPG and the “coverage gap” resulting from the use of ATPG methods employed in industry today. While the proposed method can detect nearly all CDC faults, TDF ATPG is found to be severely deficient for screening CDC faults.