Objective: There is evidence that the cholinergic system is involved in cognitive sequels of traumatic brain injury (TBI). Nicotinic acetylcholine receptors (nAChRs) are known to have a major role in cognitive functions. Smokers have up-regulation of these receptors. This study investigated whether smoking is associated with the outcome from TBI. Methods: A specific questionnaire was sent, after checking inclusion and exclusion criteria, to 1022 subjects with TBI who had visited the neurological outpatient clinic of a university hospital during a 14-year period. Of these, 689 (67.4%) responded, forming the final study population. Associations between demographic variables, injury severity and outcome and smoking history were analysed using multivariate methods. Results: Smokers were more often men (p<0.001), younger at the time of the injury (p =.008) and had less education (p<0.0001). In univariate analysis, non-smokers did not differ for outcome of TBI by GOS-E (p = 0.08). Furthermore, in multivariate analysis, no association was found between smoking history and TBI outcome. Conclusions: This study does not suggest that smoking affects the outcome of TBI.