Objective: This aim of the study was to prospectively investigate pattern of intraventricular Hemo-Dynamic Forces (HDF) associated with Left Ventricular (LV) function and remodeling in women with uncomplicated twin pregnancy. Design and method: Prospective, cohort study. Transthoracic echocardiography was performed on 35 women (aged 35.9±4.7 years) during gestation (<14 w, T1; 14–27 w, T2; >28 w, T3), and 6–7 months after delivery (T0). LV HDF were computed from echocardiography long axis data sets using a novel technique based on endocardial boundary tracking, both in apex-base (A-B) and latero-septal (L-S) directions. HDF distribution was evaluated by L-S over A-B HDF ratio (L-S/A-B HDF ratio). Results: At T1, L-S/A-B HDF ratio was higher than in T0 (p<0.05) indicating HDF misalignment. At T2, a slight impairment of cardiac function was then recorded with a reduction of Global Longitudinal Strain (GLS) and left ventricular End-Systolic Elastance (Ees) at pressure-volume relationship analysis versus T1 (both p<0.05). Finally, at T3, when HDF misalignment and LV contractility reduction (GLS and Ees) were all restored, a rightward shift of the End Diastolic Pressure-Volume Relationship (EDPVR) with an increase of ventricular capacitance were documented. Conclusions: In twin pregnancy, HDF misalignment in the first trimester precedes the slight temporary decrease in left ventricular systolic function in the second trimester; at the third trimester a rightward shift of the EDPVR was associated with a realignment of HDF and normalization of ventricular contractility indexes. These coordinated changes that occur in the maternal heart during twin pregnancy suggests the role of HDF in cardiac remodelling.