We used peak longitudinal strain (PLS) on TTE in HCM patients to differentiate LV myocardium (LVM) into the following 4 groups: group 1-no fibrosis or hypertrophy (≥ 13 mm), group 2-no fibrosis but hypertrophy evident, group 3-fibrosis present but without hypertrophy, and group 4-both fibrosis and hypertrophy. Seventeen HCM patients (13 males, 56 ± 16 years) underwent both 1.5 T CMR and TTE. On TTE, PLS (absolute values) for each LVM segment from 17 AHA-defined lesions was calculated. Of 289 LVM lesions, the numbers in each group, 1-4, were 156, 53, 39, and 41, respectively. PLS for LVM segments in group 1 (13.6 ± 6.4%) were significantly greater than those in group 2 (8.5 ± 4.9%, P < 0.001), group 3 (10.4 ± 5.0%, P = 0.006), and group 4 (7.1 ± 4.4%, P < 0.001). PLS for LVM segments in group 3 was significantly greater than those in group 4 (P = 0.016). However, significant differences in PLS in LVM between groups 2 and 3, and between 2 and 4 were not observed. Using regional PLS, we demonstrate successful differentiation of LVM in HCM patients for group 1 (LVM with zero fibrosis or hypertrophy) from LVM belonging to groups 2-4 and we also demonstrate successful differentiation of LVM with fibrosis present but without hypertrophy from LVM with both fibrosis and hypertrophy. However, it is not possible to differentiate between LVM with no fibrosis but hypertrophy evident and those with fibrosis present but without hypertrophy and also between LVM with no fibrosis but hypertrophy evident and those with both fibrosis and hypertrophy. Our findings have significant implications for the management of HCM patients.