Introduction: Recent evidence shows poor efficacy of over-the-wire balloon catheter (OTW) coronary occlusive technique adopted widely for intracoronary bone marrow stem cell (BMSC) delivery. The waterfall effect of OTW-balloon inflation/deflation with reactive ł2-fold flow velocity increase might be partly responsible for poor BMSC retention. Aim: To evaluate the safety, feasibility and tolerability of perfusion-infusion BMSC delivery with the facilitation of cell rolling in contact with the coronary endothelium (a pre-requisite for downstream transmigration). Methods: We randomly assigned 11 patients (age 41-72 years) with first anterior myocardial infarction treated with PTCA+stent and LVEF ≤45% at 6-9 days to OTW in-stent occlusive (3 x 3 min.) BMSC delivery or cell infusion via a perfusion catheter with multiple side holes (SH-PC). Results: OTW and SH-PC patients had a similar infarct size (mean peak CK 4361 vs 4717 U/L), LVEF (41.2% vs 40.3%), infused mononuclear cell number (2.99 x 10⁸ range 0.61-7.48 x 108 vs 3.28 x 10⁸ range 1.64-4.39 x 10⁸), CD 34+ number (1.79 x 10⁶ vs 1.62 x 10⁶), cell viability (91.5% vs 91.8%) and clonogenicity (CFU assay). None of the SH-PC, but 67% of OTW patients, had ST-segment elevation with chest pain (and nsVT in one) that limited OTW occlusion tolerance to 50-110 sec. At 6 months DLVEF in the OTW vs SH-PC patients was +4.2% (2-6) vs +8.8% (5-16) by MRI and +4.8 (2-7) vs +13.8% (2-24) by SPECT. Conclusions: Our work indicates that the SH-PC technique can be used safely for intracoronary BMSC transplantation. Further research is needed to determine whether the putative advantages of physiological SH-PC delivery translate into enhanced BMSC homing.