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Background: Sexual dimorphisms are well recognized in various cardiac diseases such as ischemic cardiomyopathy (ICM), hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Thorough understanding of the underlying genetic programs is crucial to optimize treatment strategies specified for each gender. By performing meta-analysis and microarray analysis, we sought to comprehensively characterize the sexual dimorphisms in the healthy and diseased heart at the level of both mRNA and miRNA transcriptome. Results: Existing mRNA microarray data of both mouse and human heart were integrated, identifying dozens/ hundreds of sexually dimorphic genes in healthy heart, ICM, HCM, and DCM. These sexually dimorphic genes overrepresented gene ontologies (GOs) important for cardiac homeostasis. Further, microarray of miRNA, isolated from mouse sham left ventricle (LV) (n = 6 & n = 5 for male & female) and chronic MI LV (n = 19 & n = 19) and from human normal LV (n = 6 & n = 6) and ICM LV (n = 4 & n = 5), was conducted. This revealed that 13 mouse miRNAs are sexually dimorphic in MI and 6 in normal heart. In human, 3 miRNAs were sexually dimorphic in ICM and 15 in normal heart. These data revealed miRNA-mRNA networks that operate in a sexually-biased fashion. Conclusions: mRNA and miRNA transcriptome of normal and disease heart show significant sex differences, which might impact the cardiac homeostasis. Together this study provides the first comprehensive picture of the genome-wide program underlying the heart sexual dimorphisms, laying the foundation for gender specific treatment strategies. [ABSTRACT FROM AUTHOR]