The study was performed to explore the predictive value of multiple strain parameters for myocardial fibrosis in patients with hypertrophic cardiomyopathy (HCM) by using speckle tracking automated functional imaging (AFI).A total of 61 patients diagnosed with HCM were finally enrolled in this study. All patients completed transthoracic echocardiography and cardiac magnetic resonance late gadolinium enhancement (LGE) within 1 month. Twenty age- and sex-matched healthy participants were included as the control group. Multiple parameters, including segmental longitudinal strain (LS), global longitudinal strain (GLS), post-systolic index and peak strain dispersion, were automatically analyzed by AFI.A total of 1458 myocardial segments were analyzed according to the left ventricular 18-segment model. Among the 1098 segments from HCM patients, segments with LGE had a lower absolute value of segmental LS than those without LGE (p < 0.05). The cutoff values of segmental LS for predicting positive LGE in the basal, intermediate and apical regions were -12.5%, -11.5% and -14.5%, respectively. GLS could predict significant myocardial fibrosis (≥2 positive LGE segments) at a cutoff value of -16.5% with a sensitivity of 80.9% and specificity of 76.5%. As an independent predictor of significant myocardial fibrosis, GLS was substantially associated with the severity of myocardial fibrosis and 5 years sudden cardiac death risk score in HCM patients.Speckle tracking AFI could efficiently identify left ventricular myocardial fibrosis in patients with HCM by multiple parameters. GLS predicted significant myocardial fibrosis at a cutoff value of -16.5%, which may indicate the adverse clinical outcomes in HCM patients.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.