Objective To investigate the expression and clinical significance of serum miR-150-5p and miR-148b-3p in elderly patients with acute ischemic stroke (AIS).Methods A total of 178 elderly patients with AIS admitted to our hospital were enrolled. According to the National Institutes of Health Stroke Scale (NIHSS), they were divided into mild group (n=52, NIHSS score <5), moderate group (n=83, 5 ≤ NIHSS score ≤ 20), and severe group (n=43, NIHSS score >20). Sixty-five healthy subjects on physical examination were selected as control group. Real-time PCR was used to determine the expression of serum miR-150-5p and miR-148b-3p in each group. A receiver operating characteristic curve was used to analyze the diagnostic value of serum miR-150-5p and miR-148b-3p levels for elderly AIS patients. Multivariate logistic regression was applied to analyze the risk factors for AIS in the elderly.Results Serum miR-125b-5p and miR-148b-3p levels were significantly lower in the AIS group than in the control group (P<0.01), and they were significantly lower in the severe group than in the moderate and mild groups (P<0.01). The optimal cut-off values of serum miR-150-5p and miR-148b-3p levels for diagnosing AIS in the elderly were 2.82 and 1.46, respectively. The area under the curve for the combination of the two indicators in diagnosis of elderly AIS was 0.927 (95% confidence interval[CI]:0.868-0.991), with a sensitivity of 93.0% and a specificity of 86.5%. The multivariate logistic regression analysis showed that low expression of miR-150-5p (odds ratio[OR]=3.107, 95%CI:2.194-6.715) and miR-148b-3p (OR=2.602, 95%CI:1.713-4.350) were independent risk factors for AIS in the elderly.Conclusions Significantly reduced levels of serum miR-150-5p and miR-148b-3p are independent risk factors for AIS in the elderly, and can be potential biomarkers for the diagnosis of AIS in the elderly.