Exploring the relationship between genetic factors and outcome following brain injury has received increased attention in recent years. However, few studies have evaluated the influence of genes on specific sequelae of concussion. The purpose of this study was to determine how the E4 allele of the apolipoprotein E (APOE) gene influences symptom expression following sports-related concussion. Participants included 42 collegiate athletes who underwent neuropsychological testing, including completion of the Post-Concussion Symptom Scale (PCSS), within 3 months after sustaining a concussion (73.8% were evaluated within 1 week). Athletes provided buccal samples that were analyzed to determine the make-up of their APOE genotype. Dependent variables included a total symptom score and four symptom clusters derived from the PCSS. Mann-Whitney U tests showed higher scores reported by athletes with the E4 allele compared to those without it on the total symptom score and the physical and cognitive symptom clusters. Furthermore, logistic regression showed that the E4 allele independently predicted those athletes who reported physical and cognitive symptoms following concussion. These findings illustrate that E4+ athletes report greater symptomatology post-concussion than E4- athletes, suggesting that the E4 genotype may confer risk for poorer post-concussion outcome. (JINS, 2016, 22, 89-94)