The dynamic interaction between subendocardial and subepicardial fibre helices in the left ventricle (LV) leads to a twisting deformation, which has an important role in LV function. This study sought to assess the influence of cardiac shape on LV twist in the normal and dilated human heart. The study comprised 45 dilated cardiomyopathy (DCM) patients and 60 for age and gender matched healthy volunteers. Speckle tracking echocardiography was used to determine basal and apical LV peak systolic rotation (Rot_max), and instantaneous LV peak systolic twist (Twist_max). LV sphericity index was calculated by dividing the LV maximal long-axis internal dimension by the maximal short-axis internal dimension at end-diastole. A parabolic relation between the sphericity index and apical Rot_max or Twist_max was identified in the total study population (R² = 0.56, and R² = 0.54, respectively, both P <0.001) and healthy volunteers (R² = 0.39, and R² = 0.25, respectively, both P <0.001), whereas these relations were linear in DCM patients (R² = 0.40, and R² = 0.43, respectively, both P <0.001). In a multivariate analysis, LV sphericity index was the strongest independent predictor of apical Rot_max and Twist_max. LV apical rotation and twist are significantly influenced by LV configuration. Taken the important function of LV twist into account, this finding highlights the vital influence of cardiac shape on LV systolic function.