Adoptive transfer of bone marrow stem cells (BMCs) for treatment of myocardial infarction has effectively improved cardiac function in several preliminary human clinical trials, but explanation of the mechanism is largely contested. In mouse models, BMCs have mediated cardiac repair after intramyocardial injection through direct and indirect reparations, but the large question remains is as to the survivability of injected cells. In this study, a veritable adult stem cell population, c-kit+ BMCs, were genetically engineered to over-express the cardioprotective kinase Pim-1 to enhance their survival in vitro as well as in vivo. Pim-1 modified BMCs (BMCeP) demonstrated increased proliferation and viability compared to un-modified BMCs (BMCe). Furthermore, BMCeP had increased resistance to apoptotic cell death with either hydrogen peroxide incubation or growth factor withdrawal as measured by flow cytometry. A comparative analysis was further performed in vivo, where after myocardial infarction, mice were intramyocardially injected with PBS, BMCe, or BMCeP and cardiac function was assessed for 12 weeks by echocardiography. At a three-week time point after injection, BMCe and BMCeP showed significant improvement in anterior wall dimensions compared to PBS and maintained this response up to 8 weeks. At a four-week time point after injection, BMCe and BMCeP had a significant improvement in fractional shortening and ejection fraction. Unfortunately, cell injected groups were not significantly different in hemodynamic parameters including heart weight body weight and function was never fully restored up to sham positive controls. Nonetheless, BMCe and BMCeP injected groups were statistically better than PBS negative controls by fractional shortening andejection fraction analysis up to 12 weeks. Although, BMCeP did not recapitulate positive effects in vivo as previously shown in our laboratory, this is attributed to the low levels of Pim-1 protein initially expressed in BMCeP. Overall, these results allude to the protective effects of genetic engineering BMCs with Pim-1 to mediate damage after myocardial infarction.