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Understanding How Long Does Prednisone Stay in Your System is important for managing its effects. Prednisone is a corticosteroid commonly prescribed for inflammation and autoimmune conditions. Its half-life is approximately 3 to 4 hours, but it can take up to 16.5 to 22 hours for your body to clear it. However, its effects may last longer. Consult your doctor for personalized information regarding prednisone usage and its duration in your system.