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Surgical site infection (SSI) is a serious complication after spine surgery. Recently, it has become possible to perform negative pressure wound therapy with instillation and dwell time (NPWTi-d) for postoperative infected wounds. We report the first rare case of symptomatic pneumoencephalopathy following NPWTi-d for methicillin-resistant Staphylococcus aureus (MRSA) infection after spinal deformity surgery.