Rationale:: Refractory angina constitutes a clinical problem. Objective:: The aim of this study was to assess the safety and the feasibility of transendocardial injection of CD133 ⁺ cells to foster angiogenesis in patients with refractory angina. Methods and Results:: In this randomized, double-blinded, multicenter controlled trial, eligible patients were treated with granulocyte colony-stimulating factor, underwent an apheresis and electromechanical mapping, and were randomized to receive treatment with CD133 ⁺ cells or no treatment. The primary end point was the safety of transendocardial injection of CD133 ⁺ cells, as measured by the occurrence of major adverse cardiac and cerebrovascular event at 6 months. Secondary end points analyzed the efficacy. Twenty-eight patients were included (n=19 treatment; n=9 control). At 6 months, 1 patient in each group had ventricular fibrillation and 1 patient in each group died. One patient (treatment group) had a cardiac tamponade during mapping. There were no significant differences between groups with respect to efficacy parameters; however, the comparison within groups showed a significant improvement in the number of angina episodes per month (median absolute difference, −8.5 [95% confidence interval, −15.0 to −4.0]) and in angina functional class in the treatment arm but not in the control group. At 6 months, only 1 simple-photon emission computed tomography (SPECT) parameter: summed score improved significantly in the treatment group at rest and at stress (median absolute difference, −1.0 [95% confidence interval, −1.9 to −0.1]) but not in the control arm. Conclusions:: Our findings support feasibility and safety of transendocardial injection of CD133 ⁺ cells in patients with refractory angina. The promising clinical results and favorable data observed in SPECT summed score may set up the basis to test the efficacy of cell therapy in a larger randomized trial.