Selection bias, common in traumatic brain injury research, limits the clinical usefulness and generalizability of study findings. The purpose of this study was to examine the effect of different inclusion and exclusion criteria on patient enrollment, and the implications for generalizability, in a mild traumatic brain injury (MTBI) study. The study was conducted at the emergency department (ED) of Tampere University Hospital. Our aim was to study outcome from MTBI in patients who do not have pre-existing conditions or other confounding factors. For this, all consecutive patients with acute head trauma (n=1344) were screened. The study design included three inclusion criteria and nine exclusion criteria. The World Health Organization Collaborating Center for Neurotrauma Task Force criteria for MTBI were used. Of all patients screened, 934 (69.5%) fulfilled the MTBI criteria. For those fulfilling the MTBI criteria, various inclusion and exclusion criteria were applied in order to yield those eligible for the outcome study. Applying these criteria excluded 95.1% of MTBI patients, leaving only 46 patients in the final sample. The final sample and the excluded patients with MTBI significantly differed in age, mechanism of injury, and injury severity characteristics. Many studies recruit fundamentally biased samples that are not generalizable to the population of persons who sustain an MTBI. Studying carefully selected samples is often necessary to address specific research questions, but such studies have serious limitations in terms of translating research findings into clinical practice.