BACKGROUND: Physiological functions with circadian rhythmicity are often disrupted during illness. OBJECTIVE: To assess the utility of circadian rhythmicity of vital signs in predicting outcome of traumatic brain injury (TBI). METHODS: A retrospective single-center cohort study of adult intensive care unit (ICU) patients with largely isolated TBI to explore the relationship between the circadian rhythmicity of vital signs during the last 24 hours before ICU discharge and clinical markers of TBI severity and score on the Glasgow Outcome Scale 6 months after injury (GOS-6). RESULTS: The 130 study participants had a median age of 39.0 years (IQR, 23.0-59.0 years), a median Glasgow Coma Scale score at the scene of 8.0 (IQR, 3.0-13.0), and a median Rotterdam score on computed tomography of the head of 3 (IQR, 3-3), with 105 patients (80.8%) surviving to hospital discharge. Rhythmicity was present for heart rate (30.8% of patients), systolic blood pressure (26.2%), diastolic blood pressure (20.0%), and body temperature (26.9%). Independent predictors of a dichotomized GOS-6 ≥4 were the Rotterdam score (odds ratio [OR], 0.38 [95% CI, 0.18-0.81]; P = .01), Glasgow Coma Scale score at the scene (OR, 1.22 [95% CI, 1.05-1.41]; P = .008), age (OR, 0.95 [95% CI, 0.92-0.98]; P = .003), oxygen saturation <90% in the first 24 hours (OR, 0.19 [95% CI, 0.05-0.73]; P = .02), serum sodium level <130 mmol/L (OR, 0.20 [95% CI, 0.05-0.70]; P = .01), and active intracranial pressure management (OR, 0.16 [95% CI, 0.04-0.62]; P = .008), but not rhythmicity of any vital sign. CONCLUSION: Circadian rhythmicity of vital signs at ICU discharge is not predictive of GOS-6 in patients with TBI.