Stem cell therapy has been used to treat ischemic cardiac disease with promising early results. However, there has been limited success using cell therapy in infarcted tissue. The cells have an inadequate microvascular environment in order to survive once implanted into scar tissue. The goal of this study was to create a microvascular environment into infarcted myocardial tissue using transmyocardial laser revascularization (TMR) as a pretreatment before cell implantation and evaluate cell survival afterwards. Balloon occlusion catheter-based myocardial infarct of the circumflex artery was created in a porcine model. The infarct was allowed to mature for 2 weeks. Three groups consisting of TMR alone (TMR), TMR + fluorescent-labeled allogeneic mesenchymal stem cells (MSCs) (TMR + Cells), and MSCs alone (Cells) were injected into the infarcted tissue using a combination TMR and cell delivery system (Phoenix, Cardiogenesis). The hearts were explanted at 1 week after treatment for cell and tissue evaluation. The myocardial infarcts were verified in all animals using both ultrasound and direct visual imaging. All arms of the study were successful with a mean of 2.0 +/- 10(6) MSCs injected per site into the scar tissue. All animals survived to explant at 1 week. On histological examination, 300 high-power fields were evaluated demonstrating that the TMR + Cells group had 25 +/- 5 cells and the Cells group 5 +/- 2 cells compared to baseline TMR alone by fluorescence. The use of TMR as a pretreatment for MSC injection increases early cell survival in infarcted tissue without increased adverse events. Further long-term functional and differentiation analysis will be required to evaluate the efficacy for future clinical translation.