Brain injury, a leading cause of mortality, morbidity and disability in the United States, has serious consequences and substantial costs. Although previous studies have assessed a variety of outcomes subsequent to brain injury, documentation of performance prior to brain injury using a case-control approach has not been included; preinjury performance differences may confound the estimate of the effects of brain injury on performance. The primary objective of this study was to compare academic performance before and after brain injury in a population of university undergraduate students to determine the extent to which the academic career of the brain-injured person was altered from what would have been expected in the absence of such an injury. Cases included all undergraduate students in a major university, between the ages of 17 and 27, who incurred a brain injury requiring hospitalization between 1980 and 1984 (n = 99). Two comparison groups were used to determine whether changes in academic performance were specifically related to brain injuries or injuries in general: (1) injured controls, i.e. 121 students between the ages of 17 and 27 years, hospitalized for injuries other than to the central nervous system, and (2) uninjured academic controls, i.e. 198 students without injuries requiring hospitalization during the study period, matched 2:1 to the brain-injured students by age, gender, and completed course credits categorized as <90, ≧90. Although there were no differences when the total groups, including both males and females, were compared, there was a significant pre- to postinjury decrease in the grade point average for female cases when compared to their uninjured academic controls (p < 0.02). This difference was related to the effects of brain injury, and not to the effects of injury in general. No such difference was observed for the males. There were also no differences when the total groups, including males and females, were compared relevant to return to school. However, a significantly higher proportion of the female cases, compared with their uninjured academic controls, did not return to school after their injury; similar findings were identified for the injured controls as well. Thus, these differences were not specific to brain injury but rather to injury in general. In spite of this observation, the difference between female cases who returned and those who did not return was associated with neurological deficits, especially upper left limb motor deficits, at the time of hospital discharge. The findings from this effort are suggestive of gender differences in the consequences of brain injury and serve as a basis for further studies to evaluate the magnitude of this proble