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Due to its favorable pharmacologic features, propofol is the most commonly used hypnotic agent in perioperative and intensive care settings. However, it also has adverse effects like propofol infusion syndrome and an increased risk of infection. Growing evidence suggests that propofol may worsen clinical outcomes by inhibiting the organ-protective properties of other interventions, such as volatile anesthetics or remote ischemic preconditioning. This editorial describes possible mechanisms underlying the detrimental effects of propofol, and provides an overview of the results of clinical trials evaluating the effects of propofol in various settings.