Although T cells are known to be involved in the pathogenesis of coronary artery disease, it is unclear which subpopulation of T cells contributes to pathogenesis in acute myocardial infarction (MI). We studied the immunological characteristics and clinical impact of CD8(+)CD57(+) T cells in acute MI patients. The frequency of CD57(+) cells among CD8(+) T cells was examined in peripheral blood sampled the morning after acute MI events. Interestingly, the frequency of CD57(+) cells in the CD8(+) T-cell population correlated with cardiovascular mortality 6 months after acute MI. The immunological characteristics of CD8(+)CD57(+) T cells were elucidated by surface immunophenotyping, intracellular cytokine staining and flow cytometry. Immunophenotyping revealed that the CD8(+)CD57(+) T cells were activated, senescent T cells with pro-inflammatory and tissue homing properties. Because a high frequency of CD8(+)CD57(+) T cells is associated with short-term cardiovascular mortality in acute MI patients, this specific subset of CD8(+) T cells might contribute to acute coronary events via their pro-inflammatory and high cytotoxic capacities. Identification of a pathogenic CD8(+) T-cell subset expressing CD57 may offer opportunities for the evaluation and management of acute MI.