Introduction: Emerging evidence suggests that accumulated bouts of non-invasive brain stimulation can improve motor performance with retention lasting months following stimulation. However, improved motor performance following stimulation is not homogenous between all participants and the underlying physiological changes are unclear. This is of particular importance as non-invasive brain stimulation is often employed as a means to induce corticospinal plasticity and further enhance motor performance following neuromuscular injury. Therefore the aim of this study was to examine the accumulative effect of non-invasive brain stimulation on corticospinal excitability, inhibition, cortical activation and strength and whether these responses were regulated by the BDNF polymorphism. Methods: In a randomized cross-over design, changes in strength, corticospinal excitability, inhibition and cortical activation were analysed in 14 young adults who were exposed to four consecutive sessions of anodal and sham transcranial direct current stimulation (tDCS). Participants also undertook a blood sample for BDNF genotyping (N= 13). Results: Following four consecutive sessions of anodal tDCS, there was a significant increase in isometric wrist flexor strength (8% compared to 3% following sham tDCS). Transcranial magnetic stimulation revealed that anodal tDCS increased corticospinal excitability as depicted at multiple points along the stimulus–response curve (32–67%), decreased silent period duration (6–13%) and increased cortical activation (3%) compared to sham tDCS (P < 0.05). Interestingly, the magnitude of change in corticospinal excitability and silent period duration was different between genotypes, with Val/Val individuals showing a greater induction of plasticity than those with the BDNF polymorphism. Discussion: The results show that four consecutive sessions of anodal tDCS increases cortical activation which manifests itself as an improvement in strength. Interestingly, the magnitude of change in corticospinal excitability and silent period duration appear to be regulated by the BDNF polymorphism. Collectively, these findings show that accumulative bouts of anodal tDCS induce corticospinal plasticity and improve strength and the BDNF polymorphism differentially regulates the induction of corticospinal plasticity.