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The aim of this study was to assess the effect of granulocyte colony-stimulating factor (G-CSF) on left ventricular (LV) function and volumes in patients with anterior ST-elevation myocardial infarction (STEMI) and depressed LV ejection fraction (EF).Sixty consecutive patients with anterior STEMI, undergoing primary angioplasty percutaneous coronary intervention (PCI), with symptom-to-reperfusion time of 2–12 h and EF ≤45% after PCI, were randomized to G-CSF 5 μg/kg b.i.d. subcutaneously (n = 24) or placebo (n = 25) for 5 days, starting <12 h after PCI. The primary endpoint was an increase from baseline to 6 months of 5% in left ventricular ejection fraction (LVEF), as measured by magnetic resonance imaging (MRI). Co-primary endpoint was a ≥20 mL difference in end-diastolic volume (EDV). Infarct size and perfusion were evaluated with late gadolinium enhancement (LGE) and gated 99mTechnetium Sestamibi single-photon emission computed tomography (SPECT). Left ventricular EDV and end-systolic volume (ESV) increased from baseline to 6 months in the placebo group (81.7 ± 24.4 to 94.4 ± 26.0 mL/m2, P < 0.00005 and 45.2 ± 20.0 to 53.2 ± 23.8 mL/m2, P = 0.016) but were unchanged in the G-CSF group (82.2 ± 20.3 to 85.7 ± 23.7 mL/m2, P = 0.40 and 46.0 ± 18.2 to 48.4 ± 20.8 mL/m2, P = 0.338). There were no significant differences in EF or perfusion between groups. A significant reduction in transmural LGE segments was seen at 6 months in the G-CSF vs. placebo groups (4.38 ± 2.9 to 3.3 ± 2.6, P = 0.04 and 4.2 ± 2.6 to 3.6 ± 2.7, P = 0.301, respectively). Significantly more placebo patients had a change in left ventricular end-diastolic volume abovethe median (9.3 mL/m2) when reperfusion time exceeded 180 min (median time-to-reperfusion) (P = 0.0123). Severe adverse events were similar between groups.Early G-CSF administration attenuates ventricular remodelling in patients with anterior STEMI and EF ≤45% after successful PCI.