The critical role of ATP-binding cassette B1 (ABCB1) in the function of the blood-brain barrier led us to conducted this prospective study in order to investigate the clinical outcome of patients suffering from severe traumatic brain injury. A total of 182 patients with traumatic brain injury were included in our study. Genotyping of ABCB1 C3435T and G2677T/A was conducted using polymerase chain reaction-restriction fragment length polymorphism. Using multivariate-logistic regression analysis, we found that patients carrying the CT+CC genotype of ABCB1 C3435T were more likely to have a better neurological outcome when compared with the TT genotype (odds ratio = 2.71, 95% confidence interval = 1.12-6.86). However, no significant association was found between the G2677T/A polymorphism and outcome of traumatic brain injury patients. Our study provides important information regarding the prognostic value of ABCB1 C3435T, and the ABCB1 C3435T polymorphism may be used as a predictive marker for the outcome of traumatic brain injury patients.