Background: We aimed to evaluate the phenotype, function, and microRNA (miRNA)17-92 cluster expression in Vγ9Vδ2 T-cell subsets and the correlation with immune response in rheumatoid arthritis (RA) patients. Methods: Peripheral blood from 10 early RA untreated patients and 10 healthy donors (HD) was obtained. Polyclonal Vγ9Vδ2 T-cell lines were generated and analysed by flow cytometry. Analysis of miRNA17-92 cluster expression was performed by real-time polymerase chain reaction (RT-PCR), and expression of mRNA target genes was also studied. Results: A remarkable change in the distribution of Vγ9Vδ2 T-cell functional subsets was observed in the peripheral blood of RA patients compared with HD, with an expansion of effector subsets and reduction of naive cells which was accompanied by modifications in proinflammatory cytokine expression. Vγ9Vδ2 T cells with a TEM (effector memory) phenotype and producing proinflammatory cytokines were correlated with disease activity score (DAS28). The comparison of miRNA expression among Vγ9Vδ2 T-cell subsets from RA patients and HD showed a lower level of miR-106a-5p and miR-20a-5p, and a higher level of miR-21a-5p, among Vγ9Vδ2 TEM cells, and a lower level of miR-19b-3p among Vγ9Vδ2 TCM (central memory) cells was also found. These differentially expressed miRNAs correlated with higher levels of expression of interleukin (IL)-8, IL-6, and PDCD4 genes. Conclusions: Our results provide evidence for a role of miR-106a, miR-19-3p, miR-20a, and miR-21a in the regulation of Vγ9Vδ2 T-cell function in RA patients and suggest the possibility that the miRNA17-92 family and Vγ9Vδ2 T cells contribute to the pathogenesis of RA.