OBJECTIVE The intracranial hematoma volume in patients with traumatic brain injury is a key parameter for the determination of the management approach and outcome. Apolipoprotein E (APOE) epsilon 4 is reported to be a risk factor for larger hematoma volume, which might contribute to a poor outcome. However, whether APOE epsilon 4 is related to progressive hemorrhagic injury (PHI), a common occurrence in the clinical setting, remains unclear. In this study, the authors aimed to investigate the association between the APOE genotype and occurrence of PHI. METHODS This prospective study included a cohort of 123 patients with traumatic intracerebral hemorrhage who initially underwent conservative treatment. These patients were assigned to the PHI or non-PHI group according to the follow-up CT scan. A polymerase chain reaction and sequencing method were carried out to determine the APOE genotype. Multivariate logistic regression analysis was applied to identify predictors of PHI. RESULTS The overall frequency of the alleles was as follows: E2/2, 0%; E2/3, 14.6%; E3/3, 57.8%; E2/4, 2.4%; E3/4, 22.8%; and E4/4, 2.4%. Thirty-four patients carried at least one allele of e4. In this study 60 patients (48.8%) experienced PHI, and the distribution of the alleles was as follows: E2/2, 0%; E2/3, 5.7%; E3/3, 22.8%; E2/4, 2.4%; E3/4, 16.3%; and E4/4, 1.6%, which was significantly different from that in the non-PHI group (p = 0.008). Additionally, the late operation rate in the PHI group was significantly higher than that in the non-PHI group (24.4% vs 11.4%, p = 0.002). Multivariate logistic regression identified APOE epsilon 4 (OR 5.14, 95% CI 2.40-11.62), an elevated international normalized ratio (OR 3.57, 95% CI 1.61-8.26), and higher glucose level (>= 10 mmol/L) (OR 3.88, 95% CI 1.54-10.77) as independent risk factors for PHI. Moreover, APOE epsilon 4 was not a risk factor for the coagulopathy and outcome of the patients with traumatic intracerebral hemorrhage. CONCLUSIONS The presence of APOE epsilon 4, an elevated international normalized ratio, and a higher glucose level (>= 10 mmol/L) are predictors of PHI. Additionally, APOE epsilon 4 is not associated with traumatic coagulopathy and patient outcome.