Left ventricular ejection fraction (LVEF) assessment is instrumental for cardiac health diagnosis, patient management, and patient eligibility for participation in clinical studies. Due to its non-invasiveness and low operational cost, ultrasound (US) imaging is the most commonly used imaging modality to image the heart and assess LVEF. Even though 3D US imaging technology is becoming more available, cardiologists dominantly use 2D US imaging to visualize the LV blood pool and interpret its area changes between end-systole and end-diastole. Our previous work showed that LVEF estimates based on area changes are significantly lower than the true volume-based estimates by as much as 13%,1 which could lead to unnecessary and costly therapeutic decisions. Acquiring volumetric information about the LV blood pool necessitates either time-consuming 3D reconstruction or 3D US image acquisition. Here, we propose a method that leverages on a statistical shape model (SSM) constructed from 13 landmarks depicting the LV endocardial border to estimate a new patient’s LV volume and LVEF. Two methods to estimate the 3D LV geometry with and without size normalization were employed. The SSM was built using the 13 landmarks from 50 training patient image datasets. Subsequently, the Mahalanobis distance (with size normalization) or the vector distance (without size normalization) between an incoming patient’s LV landmarks and each shape in the SSM were used to determine the weights each training patient contributed to describing the new, incoming patient’s LV geometry and associated blood pool volume. We tested the pro- posed method to estimate the LV volumes and LVEF for 16 new test patients. The estimated LVEFs based on Mahalanobis distance and vector distance were within 2.9% and 1.1%, respectively, of the ground truth LVEFs calculated from the 3D reconstructed LV volumes. Furthermore, the viability of using fewer principal components (PCs) to estimate the LV volume was explored by reducing the number of PCs retained when projecting landmarks onto PCA space. LVEF estimated based on 3 PCs, 5 PCs, and 10 PCs are within 6.6%, 5.4%, and 3.3%, respectively, of LVEF estimates using the full set of 39 PCs.