Objectives: To assess whether 2 different D-dimer fibrin degradation assays - a second-generation latex immunosorbent agglutination (LIA) and an enzyme-linked immunosorbent assay (ELISA) - are predictive for the development of deep venous thrombosis (DVT) at the currently accepted level of 500μg/L of D-dimer assay during the first weeks after traumatic brain injury (TBI) and to correlate over 8 weeks the second-generation LIA assay with the ELISA assay after acute TBI. Design: A case series of persons with TBI were screened for DVT at 2 weeks (±3d) using real-time, spectral Doppler ultrasound, as well as D-dimer fibrin split products. All persons were rescreened at 4, 6, and 8 weeks (±3d) after injury using D-dimer LIA and ELISA assays. Setting: A university hospital with a directly connected comprehensive in- and outpatient rehabilitation center that are part of the Traumatic Brain Injury Model Systems. Participants: Over 3 years, 35 TBI subjects with a mean Glasgow Coma Scale score of 6.5 were consecutively enrolled into the trial while on acute care. Persons were at least 16 years of age with no history of treatment for DVT. Interventions: Not applicable. Main Outcome Measures: Data were analyzed for the levels of D-dimer and risk as established by a predictive value of 500μg/L. Changes in D-dimer values over time and within subjects were assessed by analysis of variance (ANOVA) with repeated measures, and the methods were correlated. Results: The mean LIA level at 2 weeks was 4.3mg/L and averaged 1.6mg/L at 8 weeks from injury (P=.012, ANOVA), and the ELISA dropped from 4748μg/L to 1695μg/L (P=.0022, ANOVA). Except for 1 ELISA value in 1 patient, D-dimer levels were elevated beyond 500μg/L at 2 weeks. There was a very good correlation between the LIA and the ELISA at 2, 4, 6, and 8 weeks after TBI (P<.0001). In individual cases, there were only occasional discrepancies between the LIA and ELISA methods. There were no positive DVTs at 2 weeks using ultrasound, so prediction of the sensitivity and the specificity of D-dimer with DVT was not possible. Conclusion: Using the currently recommended levels of D-dimer to predict DVT is not clinically useful in the acute TBI population. © 2003 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation.