Alterations in DNA methylation have been implicated in the development of human DCM. In this study, we performed DNA methylome analysis using the Infinium 450K HumanMethylation BeadChip and characterized 1,828 DMPs identified between the left and right ventricles. Although several studies previously demonstrated that alterations in gene expression were associated with the pathogenesis of human DCM, few studies have attempted to identify the alterations in DNA methylation underlying this pathogenesis. We revealed several novel genes involved in DCM pathogenesis at the level of the regulation of DNA methylation, and showed that the effect of DNA methylation on the regulation of gene expression is not unidirectional but is controlled by the context. Additionally, we showed that DNA methylation levels were significantly enriched in functional regulatory sites such as transcription factor binding sites (TFBSs). However, significantly reduced alterations in DNA methylation were observed in CTCF binding sites. The present study will contribute to understand the epigenetic dynamics of human DCM pathogenesis.