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Prospective, dual-center, pilot study, finds that elderly trauma patients with mild TBI who received n-acetylcysteine had less severe concussion symptoms as measured by the Rivermeade Post Concussion Symptom Questionnaire. INTRODUCTION N-acetylcysteine (NAC) may be neuroprotective by minimizing postconcussion symptoms after mild traumatic brain injury (TBI), but limited data exist. This study evaluated the effects of NAC on postconcussion symptoms in elderly patients diagnosed with mild TBI. METHODS This prospective, quasirandomized, controlled trial enrolled patients 60 years or older who suffered mild TBI. Patients were excluded if cognitive function could not be assessed within 3-hours postinjury. Patients were allocated to receive NAC plus standard care, or standard care alone, based on the trauma center where they presented. The primary study outcome was the severity of concussive symptoms measured using the Rivermeade Postconcussion Symptoms Questionnaire (RPQ). Symptoms were evaluated on days 0, 7, and 30. The RPQ scores were compared both within and between treatment groups. RESULTS There were 65 patients analyzed (NAC, n = 34; control, n = 31) with an average age of 76 ± 10 years. Baseline demographics and clinical variables were similar. No group differences in head Abbreviated Injury Scale score or Glasgow Coma Scale score were observed. Baseline RPQ scores (6 [0–20] vs. 11 [4–20], p = 0.300) were indistinguishable. The RPQ scores on day 7 (2 [0–8] vs. 10 [3–18], p = 0.004) and 30 (0 [0–4] vs. 4 [0–13], p = 0.021) were significantly lower in the NAC group. Within-group differences were significantly lower in the NAC (p < 0.001) but not control group (p = 0.319). CONCLUSION N-acetylcysteine was associated with significant improvements in concussion symptoms in elderly patients with mild TBI. These results justify further research into using NAC to treat TBI. LEVEL OF EVIDENCE Therapeutic/Care Management; Level IV.