Remote ischemic conditioning (RIC) has shown an impressive neuroprotective effect on acute ischemic stroke (AIS) in animal experiments. But whether chronic RIC improves long-term functional outcomes remains unclear.We performed a non-randomized controlled trial. Eligible patients (aged 18 -80 y) with hemiplegia caused by AIS were allocated to the RIC group and the control group. All participants received normal protocol rehabilitation therapy. Patients in the RIC group underwent RIC twice daily for 90 days. The outcome included the 90-day Fugl-Meyer Assessment (FMA) scores and modified Rankin's scale (mRS) scores, as well as changes in angiogenesis-related factors in serum from baseline to 90 days.Twenty-seven patients were included in the analysis (13 in the RIC group and 14 in the control group). There was no significant difference in 90-day total FMA scores between the two groups. Lower limb FMA scores at day 90 were significantly higher in the RIC group (32.8±8.7 vs. 24.8±5.4, adjusted P=0.042). The proportion of favorable outcome (mRS<2) was higher in the RIC group than that in the control group, but no significant difference was detected (8 [61.5%] vs. 7 [50%], P=0.705). A significant increase has been found in the level of epidermal growth factor (EGF) in serum (9.4 [1.1 to 25.7] vs. -8.7 [-15.1 to 4.7], P=0.036) after chronic RIC procedure.This study investigated the role that RIC plays in AIS recovery, especially in motor function. RIC may have beneficial effects on lower limbs recovery by enhancing the EGF level. The effect of RIC on motor recovery should be further validated in future studies.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.