- Traumatic brain injury (TBI) is a major cause of death and disability. In this study a new method to measure cell free DNA (CFD) for the management of TBI is tested. Our hypothesis was that CFD concentrations correlate to the magnitude of brain damage, and may predict the outcome of injured patients. Twenty eight patients with isolated head injury were enrolled. Their demographic and clinical data were recorded. CFD levels were determined in patients' sera samples by a direct fluorescence method developed in our laboratory. Mean admission CFD values were lower in patients with mild TBI compared to severe injury (760 +/- 340 ng/ml vs. 1600 +/- 2100 ng/ml, p = 0.03), and in patients with complete recovery upon discharge compared to patients with disabilities (680 +/- 260 ng/ml vs. 2000 +/- 2300 ng/ml, p = 0.003). Patients with high CFD values had a relative risk to require surgery of 1.5 (95 % CI 0.83 to 2.9) a relative risk to have impaired outcome on discharge of 2.8 (95 % CI 0.75 - 10), and a longer length of stay(12 +/- 13 days vs. 3.4 +/- 4.8 days, p = 0.02). CFD values did not correlate with CT scan based grading. CFD levels may be used as a marker to assess the severity of TBI and to predict the prognosis. Its use should be considered as an additional tool along with currently used methods or as a surrogate for them in limited resources environment.