Background. The prognosis of traumatic brain injury is quite variable and not fully explained by the known factors. This study is to examine if the polymorphism of apolipoprotein E (apoE) influences the outcome of traumatic brain injury. Methods. Over a period of twelve months, we prospectively studied 100 patients who sustained traumatic brain injuries and were admitted to our neurosurgical unit. Findings. Nineteen patients were apoE4(+) and 81 patients were apoE4(). There was no significant difference between apoE4(+) and apoE4() groups in the cause of injury (p=0.288), type of brain injury (p=0.983) and choice of treatment (p=0.88). The proportion of patients with a lower GCS (13), indicating a poor prognosis, was higher in the apoE4(+) group (73.7%) than that in apoE4() group (61.7%), although the difference was not significant (p=0.654). Six patients (7.4%) in the apoE4() group and 5(26.3%) in the apoE4(+) group had been drinking alcohol at the time of injury (p=0.018). The mean duration of hospital stay for apoE4(+) patients was significantly longer than for apoE4() patients (p0.001). Six months after injury, 10 of 19 patients (52.6%) with apoE4 had an unfavorable outcome (dead, vegetative state, or severe disability) compared with 20 of the 81 (24.1%) patients without apoE4 (p=0.017). The apoE4(+) patients had a significantly longer hospital stay and unfavorable outcomes after brain injury. Interpretation. This study discloses a significant genetic association between the apoE genotypes and outcomes of traumatic brain injury. Patients with apoE4 allele are more likely to have an unfavorable clinical outcome after brain injury.