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In situ simulation is the practice of simulation in the actual clinical environment and has demonstrated utility in the assessment of system processes, identification of latent safety threats, and improvement in teamwork and communication. Nonetheless, performing simulated events in a real patient care setting poses potential risks to patient and staff safety. One integral aspect of a comprehensive approach to ensure the safety of in situ simulation includes the identification and establishment of “no-go considerations,” that is, key decision-making considerations under which in situ simulations should be canceled, postponed, moved to another area, or rescheduled. These considerations should be modified and adjusted to specific clinical units. This article provides a framework of key essentials in developing no-go considerations.