Purpose To develop a clinically feasible whole-heart free-breathing diffusion-tensor (DT) magnetic resonance (MR) imaging approach with an imaging time of approximately 15 minutes to enable three-dimensional (3D) tractography. Materials and Methods The study was compliant with HIPAA and the institutional review board and required written consent from the participants. DT imaging was performed in seven healthy volunteers and three patients with pulmonary hypertension by using a stimulated echo sequence. Twelve contiguous short-axis sections and six four-chamber sections that covered the entire left ventricle were acquired by using simultaneous multisection (SMS) excitation with a blipped-controlled aliasing in parallel imaging readout. Rate 2 and rate 3 SMS excitation was defined as two and three times accelerated in the section axis, respectively. Breath-hold and free-breathing images with and without SMS acceleration were acquired. Diffusion-encoding directions were acquired sequentially, spatiotemporally registered, and retrospectively selected by using an entropy-based approach. Myofiber helix angle, mean diffusivity, fractional anisotropy, and 3D tractograms were analyzed by using paired t tests and analysis of variance. Results No significant differences (P > .63) were seen between breath-hold rate 3 SMS and free-breathing rate 2 SMS excitation in transmural myofiber helix angle, mean diffusivity (mean ± standard deviation, [0.89 ± 0.09] × 10-3 mm2/sec vs [0.9 ± 0.09] × 10-3 mm2/sec), or fractional anisotropy (0.43 ± 0.05 vs 0.42 ± 0.06). Three-dimensional tractograms of the left ventricle with no SMS and rate 2 and rate 3 SMS excitation were qualitatively similar. Conclusion Free-breathing DT imaging of the entire human heart can be performed in approximately 15 minutes without section gaps by using SMS excitation with a blipped-controlled aliasing in parallel imaging readout, followed by spatiotemporal registration and entropy-based retrospective image selection. This method may lead to clinical translation of whole-heart DT imaging, enabling broad application in patients with cardiac disease. © RSNA, 2016 Online supplemental material is available for this article.