Computed tomography (CT) of the head has become the diagnostic tool of choice, particularly for moderate and severe traumatic brain injury (TBI). Various CT characteristics are associated with outcome, and may therefore be used as outcome predictors. One of the most prominent predictors appears to be the status of the basal cisterns. This study describes the prognostic value of the appearance of individual cisterns and ventricles in relation to that of the basal cisterns. Further, we determine the interrater and intrarater reliability in the evaluation of the cisterns and ventricles. All consecutive moderate and severe adult TBI patients admitted to our hospital were included in this study as part of the prospective Radboud University Brain Injury Cohort Study (RUBICS). Outcome was assessed at 6 months post-trauma using the Glasgow Outcome Scale-Extended (GOS-E). The predictive value of cisterns and ventricles was determined using multivariate binary logistic regression analysis. We included 126 moderate and 574 severe TBI patients. Absence (complete obliteration), but also compression of the ambient cisterns and/or the fourth ventricle were strongly related to unfavorable outcome and death and emerged as the only significant outcome predictors after multivariate analysis. The assessment of the ambient cisterns and the fourth ventricle had a satisfactory inter- and intrarater reliability (kappa coefficients: 0.80-0.95). We conclude that, because obliteration of the ambient cisterns and the fourth ventricle both are better than the status of the basal cisterns as outcome predictors, they might be used in CT prediction models in cases of moderate and severe TBI.