The aim of this study was to examine the potential usefulness and clinical relevance of a novel left atrial (LA) filling index using 2D speckle-tracking transthoracic echocardiography to estimate left ventricular (LV) filling pressures in patients with preserved LV ejection fraction (LVEF). The LA filling index was calculated as the ratio of the mitral early-diastolic inflow peak velocity (E) over LA reservoir strain (i.e. E/LA strain ratio). This index showed a good diagnostic performance to determine elevated LV filling pressures in a test-cohort (n = 31) using invasive measurements of LV end-diastolic pressure (area under the curve 0.82, cut-off > 3.27 = sensitivity 83.3%, specificity 78.9%), which was confirmed in a validation-cohort (patients with cardiovascular risk factors; n = 486) using the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging criteria (cut-off > 3.27 = sensitivity 88.1%, specificity 77.6%) and in a specificity-validation cohort (patients free of cardiovascular risk factors, n = 120; cut-off > 3.27 = specificity 98.3%). Regarding the clinical relevance of the LA filling index, an elevated E/LA strain ratio (>3.27) was significantly associated with the risk of heart failure hospitalization at 2 years (odds ratio 4.3, 95% confidence interval 1.8-10.5), even adjusting this analysis by age, sex, renal failure, LV hypertrophy, or abnormal LV global longitudinal systolic strain. The findings from this study suggest that a novel LA filling index using 2D speckle-tracking echocardiography could be of potential usefulness and clinical relevance in estimating LV filling pressures in patients with preserved LVEF.