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Background Severe traumatic brain injury (TBI) remains a major cause of death and disability worldwide. The aim of the study was to evaluate predictors for neurological and neuropsychological long-term outcome in patients with severe TBI treated according to an intracranial pressure (ICP-) targeted therapy. Methods From 08/2005 to 12/2008, 46 patients with severe TBI and more than 12 h of intensive care treatment were included in this study. Neurological outcome was assessed with the Glasgow Outcome Scale (GOS). Neuropsychological performance assessing 9 different domains was evaluated at long-term follow-up (median 20.5 months; range 10–46). Logistic regression was used to identify favourable outcomes according to the GOS and Fisher's exact tests were used to identify predictors of severe neuropsychological impairments at follow-up. Results Twenty-nine patients were available for neuropsychological assessment at long-term follow-up. Only 2 out of 29 patients presented normal or average neuropsychological findings throughout all 9 neuropsychological domains at long-term follow-up. The percentage of a favourable outcome (GOS 4-5) increased from 13.8% at hospital discharge to 75.8% at rehabilitation discharge to 79.3% at long-term follow-up, respectively. Age ≤40 was found to be a strong predictor of favourable outcome at follow-up (OR 5.95, 95% CI 1.41 25.00, p = 0.015). The GOS at hospital discharge was not a predictor for severe impairments in any of the 9 different neuropsychological domains (all p-values were p > 0.268). In contrast, the GOS at rehabilitation discharge was found to be a predictor of severe impairments at follow-up in all but one domain assessed (all p-values less than p Conclusions The GOS at rehabilitation discharge should be regarded as a better predictor for neuropsychological impairments at long-term follow-up than the GOS at hospital discharge. Even in patients with favourable GOS after finishing a course of rehabilitation, three quarters of these patients may have at least one severe neuropsychological deficit. Therefore, it remains of paramount importance to provide long-term neuropsychological support to further improve outcome after TBI.