OBJECT: Females comprise an increasing percentage of the athlete population across all age groups, and analysis of recent literature reveals that they sustain more concussions in collegiate sports. Results of human and animal studies indicate that females may have poorer outcomes after traumatic brain injury; however, no return-to-play guideline takes sex or other individual differences into account. In the present study the authors evaluated the influence of patient sex on objective neurocognitive performance and subjective reporting of symptoms following sports-related concussion. METHODS: According to preseason baseline neurocognitive computerized testing in 2340 male and female high school and collegiate athletes, individuals who sustained sports-related concussions (155 persons) were reevaluated using an alternate form of the cognitive test. Sex differences in the magnitude of cognitive change from baseline levels and the subjective experience of symptoms were analyzed. To account for the possible protective effects of helmets, comparisons were performed among females, males with helmets, and males without helmets; none of the female athletes wore helmets. Female athletes had significantly greater declines in simple and complex reaction times relative to preseason baseline levels, and they reported more postconcussion symptoms compared with males. As a group, females were cognitively impaired approximately 1.7 times more frequently than males following concussions. Furthermore, females experienced more objective and subjective adverse effects from concussion even after adjusting for the use of helmets by some groups of male athletes (for example, in football). CONCLUSIONS: Return-to-play decisions and concussion management must be objective and made on an individual basis, including consideration of factors such as patient sex rather than relying on a one-size-fits-all guideline.