Bone marrow cell transplantation has been proposed as a novel therapeutic option for patients with coronary artery disease. This study investigated whether autologous bone marrow-derived mononuclear cell injection into the ischemic myocardium of patients with severe angina pectoris could safely reduce anginal symptoms, improve myocardial perfusion, and increase left ventricular (LV) function. In a total of 20 patients (63 +/- 10 years old; 16 men) with angina pectoris, myocardial segments with stress-induced ischemia as assessed by gated single-photon emission computed tomography were injected with 30 to 100 million mononuclear cells. Anginal symptoms, Canadian Cardiovascular Society class, and quality of life were assessed at 3 and 6 months of follow-up. At baseline and 3 months of follow-up, an exercise test, gated single-photon emission computed tomography, and magnetic resonance imaging were performed to assess exercise capacity, myocardial perfusion, and LV function. Intramyocardial injection of autologous bone marrow-derived mononuclear cells was safe. The Canadian Cardiovascular Society class improved from 3.5 +/- 0.5 at baseline to 2.4 +/- 0.6 after 3 months (p <0.01) and 2.4 +/- 0.6 after 6 months (p <0.01). The quality-of-life score improved from 52 +/- 10% to 71 +/- 10% at 3 months (p <0.01) to 73 +/- 15% at 6 months (p <0.01). The exercise capacity increased from 79 +/- 31% to 84 +/- 29% (p <0.05). Magnetic resonance imaging revealed an increased LV ejection fraction from 51 +/- 11% to 54 +/- 10% (p <0.01) and a reduced LV end-systolic volume from 97 +/- 50 to 88 +/- 42 ml (p <0.01). The wall motion score index improved from 0.36 +/- 0.32 to 0.24 +/- 0.28 (p <0.01). The number of segments with stress-induced ischemia decreased from 5.1 +/- 3.2 to 2.3 +/- 2.6 (p<0.01). In conclusion, autologous bone marrow-derived mononuclear cell injection in patients with ischemia is safe, reduces anginal symptoms, improves myocardial perfusion, and increases LV function.