Background and Purpose ST elevation myocardial infarction (STEMI) patients display endothelial dysfunction. We investigated whether endothelial glycocalyx thickness is affected in STEMI patients and may predict left ventricular performance post event. Methods We examined 278 STEMI patients and 140 matched controls. We measured: (a) perfused boundary region (PBR) of the sublingual microvessels (range 4 to 25 mu m; increased value indicates reduced endothelial glycocalyx integrity) at baseline; (b) left ventricular ejection fraction (LVEF) and global longitudinal strain (LVGLS), at baseline and at 12 months, (c) the percentage change of left ventricular end-systolic volume (Delta LVESV) at 12 months. Results Compared with matched controls, STEMI patients had higher PBR4-25 (2.11 +/- 0.17 mu m vs. 1.98 +/- 0.20 mu m, p < 0.001). In a model including age, sex, hypertension, diabetes, hyperlipidemia, smoking, family history of coronary artery disease, number of diseased vessels, location of STEMI medication, and high-sensitivity troponin T (hs-troponin), PBR4-25 was independently associated with LVEF and LVGLS at 48 hours post-MI (for LVEF: unstandardized beta coefficient: -4.71, 95% CI: -8.53 to -0.71, p = 0.019 and for LVGLS: 2.89, 95%CI: 1.63-4.16, p < 0.001). Using multivariable analysis, PBR4-25 remained a significant predictor of the percentage change in LVEF, LVGLS, and Delta LVESV at 12-month follow-up (LVEF change: unstandardized beta coefficient: -1.38, 95% CI: -1.80 to -0.96, p < 0.001; for LV GLS change: -0.66, 95% CI: -1.14 to -0.18, p = 0.007 and for Delta LVESV: 1.42, 95% CI: 0.06-2.93, p = 0.039). A PBR4-25 cut-off value of 2.29 mu m could detect LV EF less than 45% at 48 h as well as at 12 months (AUC: 0.82, p < 0.001 and AUC: 0.80; p < 0.001). Conclusion Endothelial glycocalyx assessment is associated with myocardial performance after STEMI.