Heart failure survival after diagnosis has barely changed for more than half a century. Recently, investigation has focused on differentiation of stem cells in vitro and their delivery for use in vivo as replacement cardiac contractile elements. Here we report preliminary results using mesenchymal stem cells partially differentiated to a cardiac lineage in vitro. When delivered to the canine heart on an extracellular matrix patch to replace a full-thickness ventricular defect in vivo, they improve regional mechanical function. The delivered cells were also tracked, and some became myocytes with mature sarcomeres.