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As it evolves, aviation will continue to require integration of a wide range of safety systems and practices, some of which are already in place and others that are yet to be developed. New concepts in system safety thinking have emerged to consider not only what may go wrong, but also what can be learned when things go right during commercial flight operations. Taken together, these complementary perspectives form a more comprehensive approach to system safety thinking that can help to recognize and preserve the resilient performance capabilities currently provided by humans. A need exists, however, for research methods to enable better understanding of the human contributions to aviation safety. NASA’s System-Wide Safety Project supports research on using flight simulation methods to study operator resilience and safety-producing behaviors. Building on prior NASA efforts investigating procedural non-adherences during area navigation standard terminal route arrivals, a high-fidelity commercial aviation line operational simulation (LOS) experiment has been designed to study how flight crews anticipate, monitor for, respond to, and learn from expected and unexpected disturbances during these operations. A diverse set of LOS scenarios were developed to simulate highly realistic, complex, but routinely encountered operational situations. Each scenario provided multiple opportunities to collect data on how flight crews manage threats and errors, as well as novel opportunities to observe resilient and safety-producing behaviors. The experimental design, implications for the study of safety-producing behaviors using simulation, and considerations for airline pilot training will be discussed.