Aim To explore the changes of serum microRNA-590 (miR-590) level and its relationship with prognosis in patients with acute ischemic stroke (AIS). Methods 176 patients with AIS who received intravenous thrombolysis and arterial thrombectomy from February 2019 to October 2020 were selected as the research objects. According to the modified Rankin scale (mRS) score 90 days after treatment, the patients were divided into good prognosis group (n＝123; mRS score 0～2 points) and poor prognosis group (n＝53; mRS score 3～6 points). The level of serum miR-590 in patients with AIS was detected by real-time fluorescence quantitative PCR, the value of miR-590 in predicting the prognosis of AIS was evaluated by receiver operating characteristic (ROC) curve, and the risk factors of AIS prognosis were analyzed by Logistic regression. Results The age, male ratio, diabetes history, fasting plasma glucose (FPG), total cholesterol (TC), National Institute of Health Stroke Scale (NIHSS) score and door to needle time (DNT) in the poor prognosis group were higher than those in the good prognosis group (P＜0.05). After propensity score matching according to 1∶1, the relative level of miR-590 in the poor prognosis group was lower than that in the good prognosis group before treatment, the relative levels of miR-590 in the poor prognosis group and the good prognosis group after treatment were higher than those before treatment, after treatment the relative level increase degree of miR-590 in the poor prognosis group was higher than that in the good prognosis group, and the differences were statistically significant (P＜0.05). The area under the ROC curve of miR-590 predicting the prognosis of AIS before treatment was 0.793, which was higher than the difference of miR-590 (the difference between the relative levels of serum miR-590 before and after treatment) (P＜0.001). Logistic regression analysis showed that FPG, TC, NIHSS score and DNT were independent risk factors for the prognosis of AIS (P＜0.05), and the level of serum miR-590 before treatment was an independent protective factor for the prognosis of AIS (P＜0.001). Conclusion The low level of serum miR-590 before intravenous thrombolysis and arterial thrombectomy is related to poor prognosis in patients with AIS.