Objective: Hypokalemia is a frequent complication observed after traumatic brain injury (TBI).We evaluated the effect of spironolactone on preventing hypokalemia following moderate to severe TBI.Methods: Patients with moderate to severe TBI, whose Glasgow Coma Scale (GCS) scores of 9-12 and ＜9,respectively, were equally randomized into intervention and control groups, matching with severity of trauma and baseline serum level of potassium. For the intervention group, we administrated spironolactone (1 mg/kg per day)on the second day of admission or the first day of gavage tolerance and continued it for seven days. No additional intervention was done for controls. Hypokalemia (mild: 3-3.5 mg/L, moderate: 2.5-3 mg/L, and severe: ＜2.5 mg/L serum K+) and other electrolyte abnormalities were compared between the two groups at the end of the intervention.Results: Sixty-eight patients (58 males and 10 females)were included with mean age=(33.1±11.8) years, and GCS=7.6±2.8. The two groups were similar in baseline characteristics.Patients who received spironolactone were significantly less likely to experience mild, moderate, or severe hypokalemia (8.8%, 2.9%, and 0) compared with controls (29.4%, 11.7%,and 2.9%, respectively, P＜0.05). No significant difference was observed between the two groups in the occurrence of other electrolyte abnormalities, hyperglycemia or oliguria.Conclusion: Spironolactone within the first week of head injury could prevent the occurrence of late hypokalemia with no severe side effects.