We assessed whether a single intracoronary infusion of autologous bone marrow cells (BMCs) can have a sustained impact on left ventricular ejection fraction (LVEF) in patients after ST-elevation myocardial infarction (STEMI). In the BOne marrOw transfer to enhance ST-elevation infarct regeneration (BOOST) trial, 60 patients with STEMI and successful percutaneous coronary intervention were randomized to a control and a cell therapy group. As previously reported, BMC transfer led to an improvement of LVEF by 6.0% at 6 months (P = 0.003) and 2.8% at 18 months (P = 0.27). Left ventricular ejection fraction and clinical status were re-assessed in all surviving patients after 61 +/- 11 months. Major adverse cardiac events occurred with similar frequency in both groups. When compared with baseline, LVEF assessed by magnetic resonance imaging at 61 months decreased by 3.3 +/- 9.5% in the control group and by 2.5 +/- 11.9% in the BMC group (P = 0.30). Patients with an infarct transmurality > median appeared to benefit from BMC transfer throughout the 61-month study period (P = 0.040). A single intracoronary application of BMCs does not promote a sustained improvement of LVEF in STEMI patients with relatively preserved systolic function. It is conceivable that a subgroup of patients with more transmural infarcts may derive a sustained benefit from BMC therapy. However, this needs to be tested prospectively in a randomized trial.