This study aims to investigate the effect of amantadine use on neurological outcomes and mortality in patients with severe traumatic brain injury (TBI) (Glasgow coma score [GCS] between 3 and 8) who have been followed up on mechanical ventilators in the intensive care unit (ICU). Data from the hospital's electronic records were retrospectively searched. Patients over 18 years of age, with severe brain trauma (GCS between 3-8), who were treated with endotracheal intubation and invasive mechanical ventilation at admission to the ICU, and who were treated with Amantadine hydrochloride at least once in the first week of follow-up were included in the study. To evaluate the patients' neurological outcomes, the GCS and FOUR scores were used. GCS and FOUR scores were recorded on the 1st, 3rd, and 7th days of the first week. In addition, the score difference between the 1st and 7th day was calculated for both scores. The patients were divided into 2 groups: those receiving amantadine treatment (Group A, n = 44) and the control group (Group C, n = 47). The median age of all patients was 39 (18-81) (P = .425). When Group A and Group C were compared, no statistically significant results were found between the 1st, 3rd, and 7th day GCS values (P = .474, P = .483, and P = 329, respectively). However, the difference in GCS values between day 1 and day 7 (∆ GCS 7-1) was statistically significant (P = .012). Similarly, when Group A and Group C were compared, no statistically significant results were found between the 1st, 3rd, and 7th day FOUR score values (P = .948, P = .471, and P = .057, respectively). However, the FOUR score values between day 1 and day 7 (∆ FOUR score 7-1) were statistically significant (P = .004). There was no statistically significant difference among the groups in terms of ICU length of stay, duration of non-ICU hospital stay, and length of hospital stay (P = .222, P = .175, and P = .067, respectively). Amantadine hydrochloride may help improve neurological outcomes in patients with severe TBI. However, further research is needed to investigate this topic.