An 87-year-old woman with hypertension, chronic renal failure, and depressive syndrome with recent onset of manic episodes, presented at our Emergency Department for pain and functional impairment at her right lower limb after an accidental fall. Consciousness and vital signs were normal. Blood tests showed elevated levels of creatine kinase (21,662 IU/l) and signs of renal failure. Volume-expansion therapy and intravenous administration of furosemide and sodium bicarbonate were immediately started. The radiological examination evidenced a right hip prosthesis luxation. After an unsuccessful attempt at closed reduction, the patient was admitted to the trauma ward of our medical center. The patient had been on neuroleptic drugs, including clozapine and valproate, for several years. A few months earlier, she was also prescribed oral aripiprazole (15 mg qd). Creatine kinase levels increased up to 27,621 IU/l 24 hours later, while renal function continued to deteriorate. No signs of encephalopathy, muscular rigidity, hyperthermia, or autonomic dysfunction were present, thus excluding a neuroleptic malignant syndrome (NMS). Since aripiprazole had been the last neuroleptic drug to be added, its administration was discontinued. Subsequent blood tests evidenced a progressive decrease of creatine kinase levels, with concomitant amelioration of renal function. Normal creatine kinase levels were achieved 12 days after aripiprazole discontinuation. The patient underwent open reduction of the prosthesis luxation and was subsequently transferred to a rehabilitation clinic.