Left ventricular thrombus (LVT) formation is a dangerous complication to acute myocardial infarction (MI). We hypothesized that regional longitudinal strain impairment is associated with LVT formation. We included 373 prospectively enrolled patients with ST-segment elevation MI. All patients had an echocardiogram performed a median of 2 days post-MI. Using logistic regression, we investigated the relation between LVT and left ventricular (LV) speckle tracking, conventional echocardiographic measures and well-known echocardiographic features of LVT formation including LV smoke, aneurysm and valvular regurgitation. Overall, the mean age was 62 years of age, 75% were men, 5% had prior MI, and 48% had anterior infarcts. Mean LVEF was 46% and global longitudinal strain (GLS) was − 12%. Of 373 patients, 31 (8%) developed LVT on echocardiograms. Patients with LVT more frequently had anterior infarcts, prior MI, lower LVEF, lower e′, lower GLS and regional strain, and these were all associated with LVT formation in univariable analyses. In multivariable analysis (including anterior infarcts, prior MI, LVEF, e′), GLS and regional strain remained independently associated with LVT formation (GLS: OR = 1.17 (1.00–1.36), midventricular strain: OR = 1.19 (1.03–1.38), apical strain: OR = 1.12 (1.00–1.25), per 1% absolute decrease, p < 0.05 for all]. In a combined diagnostic model, including anterior infarct, impaired LVEF (< 42%) and apical strain (> − 8%), the sensitivity and negative predictive value was 100%, with a specificity and positive predictive value of 38 and 13%, respectively. In MI patients, non-anterior infarct, preserved LVEF and apical strain can rule out LVT formation. Reduced apical strain indicates a markedly increased LVT risk.