The primary aim of this study was to develop an automated technique for rapid computation of three-dimensional (3D) left ventricular displacement and Lagrange strain (circumferential, longitudinal and radial) in a high resolution field of phase data obtained with Displacement ENcoding with Stimulated Echoes (DENSE). DENSE is an emerging Magnetic Resonance Imaging (MRI) sequence with displacement information encoded in the phases of complex images through the cardiac cycle. A rapid spatiotemporal phase unwrapping algorithm consisting of computing and averaging phase angles of a series of Fourier transforms in images was implemented for obtaining 3D displacements. The meshfree numerical analysis technique of Radial Point Interpolation Method (RPIM) with multiquadrics (MQ) basis functions was used for computing Lagrange strains. RPIM was chosen to avoid the complications of element distortion and intensive remeshing associated with conventional finite element techniques. Regional 3D LV strains computed with the DENSE-RPIM framework were validated in reference to standard tagged-MRI (TMRI) in both normal subjects and in nonischemic dilated cardiomyopathy (DCM) patients. Circumferential strain differences estimated with Bland-Altman was 0.02 ± 0.05 (95% limits of agreement) from the DENSE-TMRI comparisons in normal subjects, -0.01 ± 0.06 from DENSE-TMRI comparisons in DCM patients and similar agreements were seen in longitudinal and radial strains. The good regional strain agreements between modalities in normal subjects and DCM patients validated accuracy of the DENSE-RPIM computational framework. Good agreements between modalities in DCM demonstrated the DENSE-RPIM framework’s ability to quantify myocardium dysfunction and show its potential for strain based risk stratification in cardiac diseases.