Objective To investigate the relationship between blood glucose fluctuation and the prognosis of severe traumatic brain injury patients. Methods A retrospective study involving 64 severe traumatic brain injury patients admitted to intensive care unit (ICU) was performed. The average glucose (GluAve), glucose standard deviation (GluSD) and glucose coefficient of variation (GluCV) during the first 72 hours were monitored. Data including mechanical ventilation, operation, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score and glasgow coma scale (GCS) score were also recorded. According to the 28-day outcome after admission, patients were divided into survivor group (n=38) and non- survivor group (n=26). The values of GluAve, GluSD and GluCV were compared between the two groups. Patients were allocated into three subgroups based on GluAve(<6.0，6.0～10.0,>10.0 mmol/L)as well as four subgroups on GluCV(<15%,15%～30%,30%～50%,>50%). The mortality was compared among the different subgroups. Receiver operating characteristic (ROC) curve was adopted to evaluate the application value of each blood glucose variability index on predicting mortality. Results The levels of APACHEⅡ, GluAve, GluSD and GluCV in non- survivor group were significantly higher than that in survivor group (P<0.05). The level of GCS in survivor group was significantly higher than that in non-survivor group (P<0.05). But there was no significant difference in ratio of mechanical ventilation and operation (P>0.05). With the gradual increase of GluAve and GluCV level, the mortality was raised accordingly (χ ₁²=6.841, P=0.033; χ ₂²=11.685, P=0.009). The predictive value was high when using GluSD and GluCV as predictor (areas under the ROC curve=0.823, 0.753) and was similar to APACHEⅡ score (Z=0.432, 1.279; P=0.665, 0.201). Conclusion Hyperglycemia and glucose fluctuation are firmly associated with mortality in patients with STBI and blood glucose variability may predict mortality as good as APACHEⅡ score.