Objective: Pro-inflammatory stimuli induce a variety set of microRNAs (miRs) expression that regulate long pentraxin-3 (PTX3) protein, which associates with a procoagulant state in the endothelial cells. We evaluated, for the first time in human, the association of miR-224-3p and miR-155-5p expressions with plasma PTX3 concentration and coronary microvascular obstruction (MVO) in patients with acute ST-segment elevation myocardial infarction (STEMI) with symptom onset ≤ 12 h and treated by primary angioplasty. Blood samples for miRs and PTX3 measurement were drawn at emergency department presentation, and were measured by TaqMan real-time PCR and human ELISA kit, respectively. Results: Of the 217 patients (median age: 54 years, male: 88%), 130 (60%) had angiographic MVO. Spearman analysis showed no correlation between miR-224-3p and miR-155-5p expressions with plasma PTX3 concentration. After adjustment with sex, age, diabetes mellitus, and plasma PTX3 concentration, miR-224-3p ≥ median group was associated with angiographic MVO (odds ratio, 2.60; 95% confidence interval, 1.24 to 5.44, p = 0.01). This study suggests that miR-224-3p and miR-155-5p expressions did not correlate with plasma PTX3 concentration. However, miR-224-3p expression associates with angiographic MVO following primary angioplasty for STEMI. Future studies are needed to identify the specific gene/protein related with miR-224-3p expression in MVO.