Studies have suggested that patients with severe head injury, in addition to Glasgow Coma Scale (GCS), reveal high D-dimer levels which are independently associated with increased mortality. In the present review, we analyzed the literature where studies have reported the role of D-dimers as a potential biomarker in stratification and early identification of patients with TBI who are at risk of clinical deterioration, where early intervention can improve overall outcomes. After scrutinizing 246 articles, which were narrowed down to 38 (16 prospective, 9 retrospective, 2 RCTs, 2 case-control, 1 cross-sectional study). All these studies included 7,589 patients, in whom D-dimer was measured at different timings and in different ways. Most studies demonstrated significant changes that could be utilized for prognostication. However, we also observed instances where no significant changes were found. Unfortunately, direct comparisons were hindered by variations in the methods used to measure D-dimer across different outcomes. Limitations included the lack of a substantial number of RCTs, heterogeneity of available data, and the difficulty in summarization of specific cutoff points for D-dimer. Future studies, especially RCTs, should measure D-dimer levels at different times from injury for an accurate assessment of its correlation with outcomes.