Objective: Hematological abnormalities after severe traumatic brain injury (TBI) are common, and are associated with a poor outcome. Whether these abnormalities offer additional prognostic significance over and beyond validated TBI prognostic models is uncertain. Methods: This retrospective cohort study compared the ability of admission hematological abnormalities to that of the IMPACT (International Mission for Prognosis and Analysis of Clinical Trials) prognostic model to predict 18-month neurological outcome of 388 patients who required a decompressive craniectomy after severe TBI, between 2004 and 2016, in Western Australia. Area under the receiver operating characteristic (AUROC) curve was used to assess predictors' ability to discriminate between patients with and without an unfavorable outcome of death, vegetative state, or severe disability. Results: Of the 388 patients included in the study, 151 (38.9%) had an unfavorable outcome at 18 months after decompressive craniectomy for severe TBI. Abnormalities in admission hemoglobin (AUROC 0.594, p = 0.002), plasma glucose (AUROC 0.592, p = 0.002), fibrinogen (AUROC 0.563, p = 0.036), international normalized ratio (INR; AUROC 0.645, p = 0.001), activated partial thromboplastin time (AUROC 0.564, p = 0.033), and disseminated intravascular coagulation score (AUROC 0.623, p = 0.001) were all associated with a higher risk of unfavorable outcome at 18 months after severe TBI. As a marker of inflammation, neutrophil to lymphocyte ratio was not significantly associated with the risk of unfavorable outcome (AUROC 0.500, p = 0.998). However, none of these parameters, in addition to the platelet count, were significantly associated with an unfavorable outcome after adjusting for the IMPACT predicted risk (odds ratio [OR] per 10% increment in risk 2.473, 95% confidence interval [CI] 2.061-2.967; p = 0.001). After excluding 8 patients (2.1%) who were treated with warfarin prior to the injury, there was a suggestion that INR was associated with some additional prognostic significance (OR 3.183, 95% CI 0.856-11.833; p = 0.084) after adjusting for the IMPACT predicted risk. Conclusions: In isolation, INR was the best hematological prognostic parameter in severe TBI requiring decompressive craniectomy, especially when patients treated with warfarin were excluded. However, the prognostic significance of admission hematological abnormalities was mostly captured by the IMPACT prognostic model, such that they did not offer any additional prognostic information beyond the IMPACT predicted risk. These results suggest that new prognostic factors for TBI should be evaluated in conjunction with predicted risks of a comprehensive prognostic model that has been validated, such as the IMPACT prognostic model.