BACKGROUND: Transcutaneous auricular vagus nerve stimulation (taVNS) is regarded as a potential method for recovery in stroke. The effectiveness of taVNS in acute and subacute stroke should be further discussed as previously, only a few small-scale trials have focused on chronic stroke patients. The objective of this study is to investigate the effect and safety of taVNS on upper limb motor function in subacute ischemic stroke patients. METHODS: Twenty-one subacute ischemia stroke patients with single upper limb motor function impairment were enrolled and randomly assigned to conventional rehabilitation training with real or sham taVNS, delivered for 15 consecutive days. Electrodes were fixed to the cymba conchae of the left ear with or without electrical stimulation. Conventional rehabilitation training was performed immediately after the end of real or sham taVNS by the same therapists. Baseline assessments were performed on day 0 of enrollment, and posttreatment evaluations were performed at 15 days, 4 weeks, and 12 weeks after the first intervention. The assessment included the upper limb Fugl-Meyer assessment (FMA-U), the Wolf motor function test (WMFT), the Functional Independence Measurement (FIM), and Brunnstrom stage. Heart rate (HR) and blood pressure (BP) were measured before and after each taVNS intervention. At the same time, any adverse effects were observed during the procedure. Outcomes were assessed by a blind evaluator. RESULTS: There were no significant differences in FMA-U, WMFT, FIM, and Brunnstrom scores between the two groups at baseline ( > 0.05). At the endpoint, the FMA-U, WMFT, and FIM scores were significantly higher than before treatment ( < 0.05), and there was a significantly greater improvement of those measurements in taVNS group compared with sham-taVNS group ( < 0.05). Significant improvements in FMA-U score were found between groups at follow-up. Only one case of skin redness occurred during the study. CONCLUSIONS: This study revealed that taVNS appeared to be beneficial to the recovery of upper limb motor function in subacute ischemia stroke patients without obvious adverse effects. . This trial is registered with ChiCTR1800019635 on 20 November 2018 (http://www.chictr.org.cn/showproj.aspx?proj=32961).