In metazoan, regulatory molecules tightly control gene expression. Among them, microRNAs (miRNAs) are key regulators of several important features, like cell proliferation, differentiation, and homeostasis. During miRNA biogenesis, the canonical strand that loads onto RISC can be switched, in a process called “arm switching.” Due to the miRNA-to-target pairing peculiarities, switching events can lead to changes on the gene-targeted repertoire, promoting the modulation of a distinct set of biological routes. To understand how these events affect cell regulation, we conducted an extensive and detailed in silico analysis of RNA-seq datasets from several tissues and key developmental stages of zebrafish. We identified interesting patterns of miRNA arm switching occurrence, mainly associated with the control of protein coding genes during embryonic development. Additionally, our data show that miRNA isoforms (isomiRs) play an important role in differential arm usage. Our findings provide new insights on how such events emerge and coordinate gene expression regulation, opening perspectives for novel investigations in the area.