Aims Previous trials that investigated cell therapy as an adjunctive therapy after acute myocardial infarction (AMI) have shown conflicting results. We designed a randomized controlled trial to determine the effect of intracoronary infusion of mononuclear cells from bone marrow (BM) or peripheral blood in patients with AMI. Methods and results In a multicentre trial, 200 patients with large first AMI treated with primary percutaneous coronary intervention were randomly assigned to either intracoronary infusion of mononuclear BM cells (n = 69), mononuclear peripheral blood cells (n 66), or standard therapy (without placebo infusion) (n 65). Mononuclear cells were delivered intracoronary between 3 and 8 days after AMI. Regional and global left ventricular myocardial function and volumes were assessed by magnetic resonance imaging before randomization and at 4 months, and clinical events were reported. The primary endpoint of the percentage of dysfunctional left ventricular segments that improved during follow-up did not differ significantly between either of the treatment groups and control: 38.6 +/- 24.7% in the BM group, 36.8 +/- 20.9% in the peripheral blood group, and 42.4 +/- 18.7% in the control group (P = 0.33 and P = 0.14). Improvement of left ventricular ejection fraction was 3.8 +/- 7.4% in the BM group, 4.2 +/- 6.2% in the peripheral blood group when compared with 4.0 +/- 5.8% in the control group (P = 0.94 and P = 0.90). Furthermore, the three groups did not differ significantly in changes in left ventricular volumes, mass, and infarct size and had similar rates of clinical events. Conclusion Intracoronary infusion of mononuclear cells from BM or peripheral blood following AMI does not improve regional or global systolic myocardial function in the HEBE trial. Registration The Netherlands Trial Register #NTR166 (www.trialregister.nl) and the International Standard Randomised Controlled Trial, #ISRCTN95796863 (http://isrctn.org).