We aimed to investigate whether left ventricular (LV) twist analysis can detect the extent of myocardial fibrosis in patients with hypertrophic cardiomyopathy (HCM). This prospective case-control study recruited 81 consecutive patients with HCM examined between January 2012 and April 2013. Data of 76 patients were analyzed after excluding 5 patients whose echocardiographic images were of poor quality. Healthy volunteers (n = 46) served as controls. Both groups underwent comprehensive echocardiographic examination (i.e., Bas-Rotation, AP-Rotation, LVEF, LADs, IVST, LAVi, E/Em, LVMI, advanced LV-twist analysis by speckle tracking echocardiography) and magnetic resonance imaging. Between-group differences were analyzed by independent t test; logistic regression analysis was performed to identify effect factors. No significant differences were found between baseline characteristics of HCM and control groups (all p > 0.05). HCM patients had significantly higher Bas-Rotation, AP-Rotation, LV Twist, LVEF, LADs, IVST, LAVi, E/Em and LVMI than controls (all p < 0.0001) and significantly lower LVDd and E/A (both p < 0.001). Bas-Rotation, AP-Rotation, LV-Twist, LADs, IVST, LAVi, E/Em and LVMI were significantly higher in HCM patients with fibrosis than in those without fibrosis (p < 0.001), but no significant differences in other echocardiographic parameters were found between those with and without fibrosis. Age, Bas-Rotation, AP-Rotation, LV twist, LADs, IVST, LAVi, E/A, E/Em, and LVMI were significant effect factors for fibrosis. AUROC analysis showed that LV twist had high discriminatory power to detect extent of myocardial fibrosis (AUC 0.996, 95 % CI 0.989-1.004, p < 0.001). Left ventricular twist mechanics are associated with the extent of myocardial fibrosis. LV-twist assessment by STE may be clinically useful.