This study was conducted to determine whether macrophage migration inhibitory factor (MIF) levels predict no-reflow in patients with ST-segment elevation myocardial infarction (STEMI). We included 120 STEMI patients who had received initial PCI therapy. Serial 12-lead ECGs acquired before and after primary PCI within 1-2 hours at 50 mm/sec were used to assess the ST-segment dynamics. When microcirculatory perfusion is compromised, the dynamics of ST-segment elevation resolution (STR) remain at 70% or less. No-reflow was detected using real-time myocardial perfusion imaging by myocardial blush grade assessment. MIF levels were assessed using ELISA before and after PCI. We found that the pre-PCI MIF contents did not significantly differ from the post-PCI MIF levels and that the total population of STEMI patients had higher plasma MIF contents than the group of healthy volunteers (3400 [2089.0-5571.0] pg/mL and 721 [567.3-1104.1] pg/mL, respectively, P < 0.001). MIF levels before and after PCI were significantly higher in patients with no-reflow than in those without it. According to ROC characteristics, the pre-PCI MIF levels that predicted the no-reflow condition had a well-balanced cut-off of 3663 pg/mL (sensitivity = 74%, specificity = 72%, 95% CI = 0.585-0.857; P = 0.0023). The no-reflow was predicted by pre-PCI MIF levels > 3663 pg/mL, whereas post-PCI MIF levels showed no discriminative potency for it. The no-reflow phenomena were independently predicted by female gender and pre-PCI MIF levels > 3663 pg/mL. Higher pre-PCI MIF levels (> 3663 pg/mL and > 5033 pg/mL, respectively) in STEMI patients were predictive of systolic cardiac dysfunction and the post-procedural no-reflow phenomena.