Both enzymatic dissociation of cells prior to needle-based injections and poor vascularization of myocardial infarct areas are two important contributors to cell death and impede the efficacy of cardiac cell therapy. Because these limitations could be overcome by scaffolds ensuring cell cohesiveness and codelivery of angiogenic cells, we used a chronic rat model of myocardial infarction to assess the long-term (6 months) effects of the epicardial delivery of a composite collagen-based patch harboring both cardiomyogenesis-targeted human embryonic SSEA-1+ (stem cell-derived stage-specific embryonic antigen-1 positive) cardiovascular progenitors and autologous (rat) adipose tissue-derived angiogenesis-targeted stromal cells (n = 27). Cell-free patches served as controls (n = 28). Serial follow-up echocardiographic measurements of left ventricular ejection fraction (LVEF) showed that the composite patch group yielded a significantly better preservation of left ventricular function that was sustained over time as compared with controls, and this pattern persisted when the assessment was restricted to the subgroup of rats with initial LVEFs below 50%. The composite patch group was also associated with significantly less fibrosis and more vessels in the infarct area. However, although human progenitors expressing cardiac markers were present in the patches before implantation, none of them could be subsequently identified in the grafted tissue. These data confirm the efficacy of epicardial scaffolds as cell carriers for ensuring long-term functional benefits and suggest that these effects are likely related to paracrine effects and call for optimizing cross-talks between codelivered cell populations to achieve the ultimate goal of myocardial regeneration. © 2014 Cognizant Comm. Corp.