Objective: The evidence for the effect of remote ischemic postconditioning(RIpostC) on autonomic function in patients with acute ischemic stroke(AIS) is lacking and the neural mechanism underlying the protection of RIpostC remains speculative. This trial was aimed to evaluated the efficiency of RIpostC on autonomic function in AIS patients. Design: One hundred and six AIS patients were included in this prospective, randomized, placebo-controlled trial. Patients in intervention group (n = 57) received 4 cycles of alternating inflation (cuff inflation to 200 mmHg) and deflation for 5 min on healthy upper arm once a day for 30 days. The control group underwent a sham inflation and deflation cycles. Autonomic function was evaluated by heart rate variability (HRV). Results: All HRV parameters except for the ratio of low frequency to high frequency (P = 0.101) increased significantly with time (P < 0.001) in the two groups. The value of standard deviation of all normal R-R intervals(SDNN) and high frequency at day7 and day30 and the value of the percent of difference between adjacent normal R-R intervals (pNN50) at day 30 in RIpostC group was significantly higher than that of the sham-RIpostC group(P < 0.05). A significant time-by-group interaction was observed in SDNN、pNN50、and high frequency over time between two groups (P < 0.05). Conclusions: 30-day RIpostC could improve autonomic function in AIS patients through the enhancement of the total autonomic nerve activity and vagus nerve activity. The mechanism of RIpostC mediating autonomic function needs to be further investigated. © 2020