Aims To assess the efficacy and safety of bone marrow cell (BMC) therapy after thrombolytic therapy of an acute ST-elevation myocardial infarction (STEMI). Methods and results Patients with STEMI treated with thrombolysis followed by percutaneous coronary intervention (PCI) 2–6 days after STEMI were randomly assigned to receive intracoronary BMCs (n = 40) or placebo medium (n = 40), collected and prepared 3–6 h prior PCI and injected into the infarct artery immediately after stenting. Efficacy was assessed by the measurement of global left ventricular ejection fraction (LVEF) by left ventricular angiography and 2-D echocardiography, and safety by measuring arrhythmia risk variables and restenosis of the stented vessel by intravascular ultrasound. At 6 months, BMC group had a greater absolute increase of global LVEF than placebo group, measured either by angiography (mean ± SD increase 7.1 ± 12.3 vs. 1.2 ± 11.5%, P = 0.05) or by 2-D echocardiography (mean ± SD increase 4.0 ± 11.2 vs. −1.4 ± 10.2%, P = 0.03). No differences were observed between the groups in the adverse clinical events, arrhythmia risk variables, or the minimal lumen diameter of the stented coronary lesion. Conclusion Intracoronary BMC therapy is associated with an improvement of global LVEF and neutral effects on arrhythmia risk profile and restenosis of the stented coronary lesions in patients after thrombolytic therapy of STEMI.