BACKGROUND: A noninvasive tool reflecting intracranial hypertension (ICH) should prompt early invasive monitoring and reduce secondary injury after traumatic brain injury. We hypothesized that integer heart rate variability (HRV) may be associated with rises in intracranial pressure (ICP); changes in HRV may precede changes in ICP; and both increases in ICP and cardiac uncoupling (low HRV) predict mortality. METHODS: Of 14,330 consecutive trauma admissions, 291 of these patients had an injury requiring intracranial monitoring. Of these patients 145 had simultaneous HRV and ICP monitoring with a Camino monitor. ICP and heart rate (HR) data were matched and divided into 5-minute intervals (N = 117,956, representing 24.4 million HR and ICP data points). In each interval, the median ICP, and SD of HR (HRSD5) were calculated. Cardiac uncoupling was defined as an interval with HRSD5 between 0.3 bpm and 0.6 bpm. Cardiac uncoupling was compared between ICP categories using the Wilcoxon Rank-Sum test, and logistic regression was used to assess the continuous relationship between ICP and risk of uncoupling. RESULTS: Cardiac uncoupling increases as ICP increases (p < 0.001). Uncoupling nearly doubles when comparing acceptable ICP (<20 mm Hg, 11% uncoupled) to ICH (31-50 mm Hg, 18% uncoupled), with uncoupling = 13% in the intermediate group (ICP 21-30 mm Hg). This trend continues at the level of malignant ICH (>50 mm Hg, 22% uncoupled). CONCLUSION: Cardiac uncoupling increases as ICP increases. Both cardiac uncoupling and ICH predict mortality. Cardiac uncoupling may precede ICH but is not yet an indication for invasive monitoring.