The purpose of this study was to evaluate the impact of liver cirrhosis on in-hospital outcomes in victims of isolated traumatic brain injury (TBI). This was a National Trauma Databank study over a 5-year period, including patients with isolated TBI. Propensity scores were calculated to match cirrhotic with noncirrhotic TBI patients in a 1:2 ratio. Primary outcomes included mortality, hospital and surgical intensive care unit length of stay, and ventilator days. Of the 35,005 patients with isolated TBI, 47 (0.13%) had documented liver cirrhosis. After matching with 94 noncirrhotic, isolated TBI patients, no differences with regards to demographic and clinical injury characteristics were observed comparing the two groups. The mean SICU length of stay for cirrhotic and noncirrhotic patients was 5.4 ± 8.8 days and 3.7 ± 7.0 days, respectively (P = 0.079). Cirrhotic patients experienced significantly more ventilator days compared with their noncirrhotic counterparts (2.9 ± 6.4 days vs 2.0 ± 6.4 days; P = 0.001). Overall mortality in the study population was 23.4 per cent with significantly higher in-hospital mortality among cirrhotic versus noncirrhotic TBI patients [34.0% vs 18.1%; odds ratio (95% confidence interval): 2.34 (1.05-5.20); P = 0.035]. Traumatic brain injury in conjunction with liver cirrhosis is associated with two-fold increased mortality and significantly prolonged ventilator requirements when compared with their noncirrhotic counterparts of isolated TBI.