Cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs) or directly reprogrammed from non-myocytes (induced cardiomyocytes iCMs) are promising sources for heart regeneration or disease modeling. However, the similarities and differences between iPSC-CMs and iCMs are still unknown. Here, we performed transcriptome analyses of beating iPSC-CMs and iCMs generated from cardiac fibroblasts (CFs) of the same origin. Although both iPSC-CMs and iCMs establish CM-like molecular features globally, iPSC-CMs exhibit a relatively hyperdynamic epigenetic status, whereas iCMs exhibit a maturation status that more closely resembles that of adult CMs. Based on gene expression of metabolic enzymes, iPSC-CMs primarily employ glycolysis, whereas iCMs utilize fatty acid oxidation as the main pathway. Importantly, iPSC-CMs and iCMs exhibit different cell-cycle status, alteration of which influenced their maturation. Therefore, our study provides a foundation for understanding the pros and cons of different reprogramming approaches. Display omitted •Gene expression profiling of iPSC-CMs and iCMs derived from CF of the same origin•Comparative analyses revealed distinct molecular features between iPSC-CMs and iCMs•iPSC-CMs and iCMs differ in gene signature of cell cycle, metabolism, and chromatin status•iCMs more closely resemble adult CMs when compared to iPSC-CMs Zhou et al. performed gene expression profiling of cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs) or generated through direct reprogramming (induced cardiomyocytes iCMs) from cardiac fibroblasts of the same origin. Comparative analyses revealed similarities and differences in the molecular signatures of iPSC-CMs and iCMs.