Introduction <p>Traumatic brain injury (TBI) poses a large burden and cost on the patients, being among the most prevalent causes for emergency department visits. One of the major issues with TBI is the long-term functional outcome of patients, causing disabilities affecting the patient and the surrounding members of society. Several attempts have been made in order to address functional outcomes via means such as pharmacotherapy, physical therapy, and newer methods. In this study, we aimed to conduct a double-blinded, randomized controlled trial with the administration of methylphenidate and amantadine, two drugs proven effective separately in previous studies, to evaluate the functional outcome of patients with blunt TBI.</p> Methods <p>Patients with blunt TBI were randomly assigned into treatment and control groups. Patients in the treatment group received 100&#xa0;mg of amantadine and 20&#xa0;mg of methylphenidate twice daily while patients in the control group received similarly shaped placebos. The patients age, gender, GCS, ICU and hospital length of stay and GOSE were evaluated and calculated for evaluation of outcome and initial condition. The main target was GOSE evaluated 6 months after discharge.</p> Results <p>A total of 184 patients were included in our study, randomly and equally divided into the treatment and control groups. The mean age of patients was 40.63 ± 17.46, and 84.8% of patients were male. There was no significant difference between the two groups’ age, gender, and initial GCS. Regarding outcome measures, there was no statistical difference between the groups in hospital and ICU length of stay. GOSE was significantly higher in patients in the treatment group (6.22 ± 2.06 vs. 5.37 ± 2.54, <i>p</i> = 0.014).</p> Conclusion <p>Co-administering methylphenidate and amantadine could help patients with blunt TBI, especially in long-term settings, regarding their functional outcome.</p>