© 2021 by Turkish Society of CardiologyObjective: In this study, we aimed to compare the functional adaptations of the left ventricle in variant forms of left ventricular hypertrophy (LVH) and to evaluate the use of two-dimensional speckle tracking echocardiography (2D-STE) in differential diagnosis and prognosis. Methods: This was a prospective cohort study of 68 patients with LVH, including 20 patients with non-obstructive hypertrophic cardiomyopathy (HCM), 23 competitive top-level athletes free of cardiovascular disease, and 25 patients with hypertensive heart disease (HHD). All the subjects underwent 2D transthoracic echocardiography (TTE) and 2D-STE. The primary endpoint was all-cause mortality. Global longitudinal strain (GLS) below −12.5% was defined as severely reduced strain, −12.5% to −17.9% as mildly reduced strain, and above −18% as normal strain. Results: The mean LV-GLS value was higher in athletes than in patients with HCM and HHD with the lowest value being in the HCM group (HCM: −11.4±2.2%; HHD: −13.6±2.6%; and athletes: −15.5±2.1%; p<0.001 among groups). LV-GLS below −12.5% distinguished HCM from others with 65% sensitivity and 77% specificity [area under curve (AUC)=0.808, 95% confidence interval (CI): 0.699-0.917, p<0.001]. The median follow-up duration was 6.4±1.1 years. Overall, 11 patients (16%) died. Seven of these were in the HHD group, and four were in the HCM group. The mean GLS value in patients who died was −11.8±1.5%. LV-GLS was significantly associated with mortality after adjusting age and sex via multiple analysis (RR=0.723, 95% CI: 0.537-0.974, p=0.033). Patients with GLS below −12.5% had a higher risk of all-cause mortality compared with that of patients with GLS above −12.5% according to Kaplan-Meier survival analysis for 7 years (29% vs. 9%; p=0.032). The LV-GLS value predicts mortality with 64% sensitivity and 70% specificity with a cut-off value of −12.5 (AUC=0.740, 95% CI: 0.617-0.863, p=0.012). Conclusion: The 2D-STE provides important information about the longitudinal systolic function of the myocardium. It may enable differentiation variable forms of LVH and predict prognosis.