Introduction: Llittle is known about the relationship between LA strain mechanics and exercise intolerance in hypertrophic cardiomyopathy (HCM), or whether LA strain mechanics might serve as novel imaging markers in predicting the need for septal myectomy. Hypothesis: LA mechanical dysfunction would be associated with impaired exercise capacity and clinical deterioration necessitating septal myectomy in HCM. Methods: Consecutive patients with HCM who underwent exercise stress echocardiography and cardiopulmonary exercise testing between October 2015 and April 2019 were enrolled prospectively. LA structure parameters (maximum and minimum LA volume indices) and LA function parameters were measured. LA strain mechanics (reservoir, conduit and contractile strains) were analyzed by speckle tracking echocardiography. LA stiffness was calculated as the ratio of E/e’ to reservoir strain. Based on the quartile of percent-predicted peak VO 2 , the study cohort was divided into four groups. Exercise intolerance was defined as the lowest quartile of percent-predicted peak VO 2 (≤52%). Results: Of 536 HCM patients studied (mean age: 51 ± 15 years, 42% female), 212 (40%) demonstrated exercise intolerance. Receiver operating characteristics analysis demonstrated LA contractile strain, using a cut-off of 13.8%, to be optimal for predicting exercise intolerance (AUC: 0.68, p <0.001). On multivariable logistic regression analysis, impaired LA contractile strain was an independent predictor for exercise intolerance (p <0.001). Among 258 patients who were followed up at our center, patients with LA stiffness worse than the median value (≥0.41) had significantly higher probability of requiring myectomy, compared with those with LA stiffness below the median (p = 0.02, Figure ). Conclusions: Impaired LA contractile strain was an independent predictor of exercise intolerance in HCM. Patients with worse LA stiffness were more likely to require septal myectomy.