Objective: This study aims to investigate the association of circulating miR-660-5p with no-reflow phenomenon (NRP) in patients with ST segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Methods: Consecutive patients diagnosed with anterior STEMI within 12 h of pain onset were included; in these patients, coronary angiography confirmed that the left anterior descending artery was infarcted. Angiographic NRP was defined as a final thrombolysis in myocardial infarction (TIMI) flow 2 or 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 Body Mass Index: 26.3 +/- 3.5). The incidence of NRP was 38.5%. Circulating miR-660-5p was significantly related to the mean platelet volume (MPV). The patients were grouped into tertiles by miR-660-5p levels (Q1: <7.18, Q2: 7.18-11.31, Q3: >11.31). Those in the high microRNA-660-5p group had nearly 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 analyzed by tertiles, relative odds of NRP were consistently increasing (OR1 for Q2 vs. Q1: 1.25, 95% CI: 0.27-5.73, p=0.770; OR2 for Q3 vs. Q1: 5.96, 95% CI: 1.33-26.66, p=0.02), despite 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 NRP in patients undergoing PPCI with an area under the ROC 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.