BACKGROUND: Left ventricular (LV) global longitudinal strain (GLS) has emerged as a significant prognostic marker in patients after myocardial infarction (MI). Although elevated LV filling pressure after MI might alter GLS, direct evidence for this is lacking. This study aimed to clarify the association between GLS and LV filling pressure in a large animal MI model. METHODS: A total of 104 Yorkshire pigs underwent both echocardiographic and hemodynamic assessments 1 to 4 weeks after induction of large anterior MI. GLS was measured in the apical four-chamber view using a semi-automated speckle-tracking software. LV pressure-volume relationship was invasively measured using a high-fidelity pressure-volume catheter. GLS >-14% was considered impaired. RESULTS: Compared to pigs with LV ejection fraction (LVEF) >40% and preserved GLS (n=29), those with LVEF >40% and impaired GLS (n=37) and those with LVEF ≤40% (n=38) had significantly higher LV end-diastolic pressure (15.5±5.5 vs. 19.7±5.8 and 19.6±6.6 mmHg; P=0.008 and P=0.026, respectively) and higher LV mean diastolic pressure (7.1±2.9 vs. 10.4±4.5 and 11.1±5.4 mmHg; P=0.013 and P=0.002, respectively). GLS was modestly correlated with tau (r=0.21, P=0.039) and slope of LV end-diastolic pressure-volume relationship (r=0.43, P<0.001). Impaired GLS was associated with higher LV end-diastolic and mean diastolic pressures after adjusting for LVEF and baseline characteristics (P=0.026 and P=0.001, respectively). CONCLUSIONS: Impaired GLS assessed by speckle-tracking echocardiography was associated with elevated LV filling pressure after MI. GLS has an incremental diagnostic value for detecting elevated LV filling pressure and may be particularly useful for evaluating post-MI patients with preserved LVEF.