Reproductive performance in dairy cows is a major factor determining herd efficiency and profitability. The objective of this study was to evaluate the effect of dietary organic minerals on gene expression profiles of endometrial tissue. A total of 18 Holstein heifers (10–15 mo) were randomly assigned to 2 groups (n = 9/treatment) and supplemented for 90d with an organic premix (consisting of Bioplex Zn, Bioplex Cu, Bioplex Mn and EconomasE) or a standard inorganic premix (control). Endometrium was biopsied at d90 of supplementation and RNA was hybridized to the Affymetrix Bovine Genome Array. Hierarchical clustering analysis resulted in 2 different groups as a function of the pairwise distances corresponding to the treatments. Relative expression analysis between treatments resulted in a total of 580 differentially expressed genes (P < 0.05; 398 upregulated; 182 downregulated), which enriched (P < 0.05) different pathways related to reproductive performance: (1) Dendritic cell maturation, which regulates endometrium cell differentiation and the vascular responses associated with implantation; (2) Relaxin hormone signaling, which confers beneficial effects on the endometrium for implantation; (3) Gaq signaling function of smooth muscle tissue like endometrium; and (4) Thrombin signaling, which promotes coagulation and the binding and aggregation of platelets and facilitating the rapid adherence of neutrophils, monocytes and lymphocytes to the endothelial cell layer to overcome exogenous challenge or play an essential role in early pregnancy. In conclusion, supplementation with organic minerals potentially benefits reproductive performance, including improved regulation of the estrous cycle, shorter calving intervals, and improved implantation rates.