Displacement encoding using stimulated echoes (DENSE) and spatial modulation of magnetization (SPAMM) are MRI techniques for quantifying myocardial displacement and strain. However, DENSE has not been compared against SPAMM in phantoms exhibiting nonhomogeneous strain, and interobserver variability has not been compared between DENSE and SPAMM. To perform these comparisons, there is a need for a generalized analysis framework for the evaluation of myocardial strain. A spatiotemporal mathematical model was used to represent myocardial geometry and motion. The model was warped to each frame using tissue displacement maps calculated from either automated phase unwrapping (DENSE) or nonrigid registration (SPAMM). Strain and motion were then calculated from the model using standard methods. DENSE and SPAMM results were compared in a deformable gel phantom exhibiting known nonhomogeneous strain, and interobserver errors were determined in 19 healthy human volunteers. Nonhomogeneous strain in the phantom was accurately quantified using both DENSE and SPAMM. In the healthy volunteers, DENSE produced better interobserver errors than SPAMM for radial strain (−0.009 ± 0.069 vs. 0.029 ± 0.152, respectively, bias ±95% confidence interval). In conclusion, generalized spatiotemporal modeling enables robust myocardial strain analysis for DENSE or SPAMM. Magn Reson Med, 2011. © 2011 Wiley-Liss, Inc.