Objective To investigate the therapeutic effect of limb ischemic post-conditioning (RIPostC) on acute cerebral infarction and its impact on cognitive function after cerebral infarction, and to explore the appropriate treatment regimen. Methods Non-thrombolysis patients with acute anterior circulation infarction were recruited within 72 hours after onset and randomly divided into four groups, namely RIPostC 10d group, RIPostC 14d group, 10d control group, and 14d control group. Four cycles of inflation and deflation were performed in each group. National Institute of Health Stroke Scale (NIHSS) score, cerebral infarct volume (on admission and at 10 days, 14 days, and 90 days), modified Rankin Scale (mRS) score (admission score, and rate of good prognosis at 90 days), Mini-mental State Examination (MMSE) score, and Montreal Cognitive Assessment Scale (MoCA) score (cognitive impairment rates at 14 days and 90 days) were compared. Results Eighty-nine eligible patients with acute cerebral infarction (44 cases in the RIPostC group and 45 cases in the control group) were enrolled. In the RIPostC 10d group, only one patient could not tolerate and gave up treatment, while the control group was completely tolerant. In the control group, 3 patients had recurrent cerebral infarction at 30 days, 65 days, and 78 days, respectively, but no related cardiovascular and cerebrovascular events occurred in each RIPostC group. At 90 days, the RIPostC 10d and 14d groups had significant decreases in the NIHSS score (P<0.05) and significant reductions in the infarct volume (33.7% and 37.2%, P<0.05) compared with the 10d and 14d control groups. In addition, these two groups also had significant increases in the good prognosis rate of mRS (P<0.05) and significant decreases in the rates of MMSE and MoCA cognitive impairment. There were no significant differences in the NIHSS score and the good prognosis rate of mRS between the RIPostC 14d group and the RIPostC 10d group (P>0.05). Conclusions RIPostC is well tolerated, safe, and feasible after acute cerebral infarction, which can reduce the cerebral infarct volume and disability, and also improve prognosis. Meanwhile, it can alleviate cognitive impairment after cerebral infarction. However, RIPostC 10 days and 14 days are not significantly different regarding the treatment of cerebral infarction and their impact on cognitive function. Therefore, RIPostC 10 days is the appropriate treatment regimen for this study.