The brain-derived neurotrophic factor (BDNF) is involved in neurogenesis and formation of regenerated myofibers following injury or damage. Recent study suggests that the BDNF overexpression increases the proportion of fast-twitch muscle fibers, while the BDNF deletion promotes a fast-to-slow transition. The purpose of this study was to evaluate the association between the BDNF gene rs10501089 polymorphism (associated with blood BDNF levels), muscle fiber composition and power athlete status. Muscle fiber composition was determined in 164 physically active individuals (113 males, 51 females). BDNF genotype and allele frequencies were compared between 508 Russian power athletes, 178 endurance athletes and 190 controls. We found that carriers of the minor A-allele (the BDNF-increasing allele) had significantly higher percentage of fast-twitch muscle fibers than individuals homozygous for the G-allele (males: 64.3 (7.8) vs. 50.3 (15.8)%, P = 0.0015; all participants: 64.1±7.9 vs. 49.6±14.7%, P = 0.0002). Furthermore, the A-allele was associated (P = 0.036) with greater handgrip strength in a sub-group of physically active subjects (n = 83) and over-represented in power athletes compared to controls (7.7 vs. 2.4%, P = 0.0001). The presence of the A-allele (i.e., AA+AG genotypes) rather than GG genotype increased the odds ratio of being a power athlete compared to controls (OR: 3.43, P = 0.00071) or endurance athletes (OR: 2.36, P = 0.0081). In conclusion, the rs10501089 A-allele is associated with increased proportion of fast-twitch muscle fibers and greater handgrip strength, and these may explain, in part, the association between the AA/AG genotypes and power athlete status.