To elucidate whether Macrophage Migration Inhibitory Factor (MIF) levels anticipate no-reflow among ST-segment Elevation Myocardial Infarction (STEMI) patients. We enrolled 120 STEMI individuals given treatment with initial PCI. Assessment of the ST-segment dynamics was performed with serial 12-lead ECGs obtained before and after primary PCI within 1-2 hours at 50 mm/sec. In the case of impaired microcirculatory perfusion, the dynamics of ST-segment elevation resolution (STR) remain equal to 70% or less. The real-time myocardial perfusion imaging with myocardial blush grade determination was used to identify no-reflow. ELISA measured the levels of MIF before and after PCI. We found that higher plasma MIF contents were indicated in the entire STEMI patients’ population when compared to the healthy volunteers’ group (3400 [2089.0-5571.0] pg/mL and 721 [567.3-1104.1] pg/mL respectively, р<0.001), and the pre-PCI MIF contents did not substantially distinguish from post-PCI MIF levels. Patients with no-reflow had significantly higher pre-PCI and post-PCI MIF levels than those who did not have it. ROC characteristics showed that well-balanced cut-off of pre-PCI MIF levels that predicted the no-reflow condition was 3663 pg/mL (sensitivity =74%, specificity =72%, 95% CI=0.585-0.857; p = 0.0023). Pre-PCI MIF levels > 3663 pg/mL predicted the no-reflow, whereas post-PCI MIF levels did not demonstrate a discriminative potency for it. The pre-PCI MIF levels > 3663 pg/mL and female gender were independent predictors for the no-reflow phenomenon. In STEMI patients, elevated pre-PCI MIF levels (>3663 pg/mL and >5033 pg/mL, respectively) predicted post-procedural no-reflow phenomenon and systolic cardiac dysfunction.