The focus of this paper is to identify and quantify risk factors for early hemorrhagic progression of brain contusions (HPC) in patients with traumatic brain injury (TBI) and to evaluate their impact on patients' outcome. Further, based on abnormal values in routine blood tests, the role of trauma-induced coagulopathy is analyzed in detail. Therefore, a prospective study of 153 TBI patients was completed at one institution between January 2008 and June 2012. The collected data included demographics, initial Glasgow Coma Scale pupillary response, initial and 6 h follow-up computed tomography scan findings, coagulation parameters (international normalized ratio, partial thromboplastin time, platelet count, fibrinogen, D-dimer and factor XIII), as well as outcome data using the modified Rankin score at discharge and after one year. The overall rate of early HPC within the first 6 h was 43.5%. The frequency of coagulopathy was 47.1%. When analyzing for risk factors that independently influenced outcome in the form of mRS ≥4 at both points, the following variables appeared: elevated D-dimer level (≥10,000 μg/L), HPC, and initial brain contusions ≥3 cm. Patients sustaining early HPC had a hazard ratio of 5.4 for unfavorable outcome at discharge (p=0.002) and of 3.9 after one year (p=0.006). Overall, patients who developed early HPC were significantly more likely to be gravely disabled or to die. Unfavorable neurological outcome after an isolated TBI is determined largely by early HPC and coagulopathy, which seem to occur very frequently in TBI patients, irrespective of the severity of the trauma.