Background: The no-reflow phenomenon (NRP) is an important factor affecting the prognosis of patients with acute myocardial infarction undergoing primary percutaneous coronary intervention (PPCI). This study aims to investigate the association of circulating miR-660-5p with NRP in patients with ST segment elevation myocardial infarction (STEMI) undergoing PPCI.Methods: Consecutive patients diagnosed with anterior STEMI within 12 h of pain onset were included in the study; in these patients, coronary angiography confirmed that the infarct-related artery was the left anterior descending (LAD) artery. Angiographic NRP was defined as a final TIMI flow of 2 or a final TIMI flow of 3 with a myocardial blush grade (MBG) < 2. High miR-660-5p was defined as a value in the third tertile. The relationship of circulating miR-660-5p with NRP was assessed using Spearman correlation analysis and multiple logistic regression analysis.Results: Fifty-two eligible patients were finally included in this study (mean age: 56±12.4 years, >65 years: 53.8%, male: 76.9%, and mean BMI: 26.3±3.5). The incidence of NRP was 38.5%. Circulating miR-660-5p was significantly related to the mean platelet volume (MPV). Patients were divided into tertiles by miR-660-5p levels (Q1: ≤ 7.18, Q2: 7.18-11.31, Q3: > 11.31). Patients in the high microRNA-660-5p group had almost a 6-fold higher risk of NRP than those in the low microRNA-660-5p group [(odds ratio (OR)=5.68, 95% confidence interval (CI) 1.40-23.07, p=0.015). When analysed by tertiles, consistent trends of an increasing relative odds of NRP were reported (OR1 for Q2 VS. Q1: 1.25, 95% CI: 0.27-5.73, p=0.77; OR2 for Q3 VS. Q1: 5.96, 95% CI: 1.33-26.66, p=0.02), even after multivariable adjustment. Receiver operating characteristic curve analysis demonstrated that the microRNA-660-5p level of 10.17 was the best cut-off level to predict the incidence of the no-reflow phenomenon in patients undergoing primary percutaneous coronary intervention with an area under the curve (AUC) of 0.768 (95% CI: 0.636-0.890).Conclusion: Circulating miR-660-5p was significantly associated with NRP, and it may be a useful biomarker to predict the incidence of NRP in patients with STEMI undergoing PPCI.