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Abstract De-implementing inappropriate health interventions is essential for minimizing patient harm, maximizing efficient use of resources, and improving population health. Research on de-implementation has expanded in recent years as it cuts across types of interventions, patient populations, health conditions, and delivery settings. This commentary explores unique aspects of de-implementing inappropriate interventions that differentiate it from implementing evidence-based interventions, including multi-level factors, types of action, strategies for de-implementation, outcomes, and unintended negative consequences. We highlight opportunities to continue to advance research on the de-implementation of inappropriate interventions in health care and public health.