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The story of Ignaz Semmelweis suggests a lesson to beware of unintended consequences, especially with in situ simulation. In situ simulation offers many important advantages over center-based simulation such as learning about the real setting, putting participants at ease, saving travel time, minimizing space requirements, involving patients and families. Some substantial disadvantages include frequent distractions, lack of privacy, logistics of setup, availability of technology, and supply costs. Importantly, in situ simulation amplifies some of the safety hazards of simulation itself including maintaining control of simulated medications and equipment, limiting the use of valuable hospital resources, preventing incorrect learning from simulation shortcuts, and profoundly upsetting patients and their families. Mitigating these hazards by labeling effectively, publishing policies and procedures, securing simulation supplies and equipment, educating simulation staff, and informing participants of the risks are all methods that may lessen the potential for an accident. Each requires a serious effort of analysis, design, and implementation.