Objective Basic science studies demonstrated a general intramyocardial angiogenetic response potentially responsible for the creation of a microvascular neocapillaries network assisting myocardial function. We hypothesized that the benefit provided by the reperfusion of left anterior descending (LAD) territories and the biological angiogenetic drive triggered by the revascularization could translate in a global improvement in ventricular contractility, not restricted to the grafted area. Methods High-risk patients with multivessel coronary artery disease and preoperative wall motion abnormalities were retrospectively analysed to compare outcomes and regional ventricular function of those who received optimal medical therapy (OMT) versus those who underwent off-pump coronary artery bypass grafting (CABG) and received an incomplete myocardial revascularization using left internal mammary artery (LIMA) on LAD (off-pump CABG group). From January 2007 to December 2014, 206 patients (OMT n = 136, OPCAB n = 70) were propensity-score matched to have 70 matched pairs. Variables included in propensity score analyses were ejection fraction (EF), left ventricular end diastolic volume (LVEDVi), EuroSCORE II. Primary endpoint was the variation in the global wall motion score index (ΔWMSI) as evaluated by transthoracic echocardiography. Follow up was completed at 3 years from surgery or hospital discharge. Results Regional analysis of ventricular function revealed a regional WMSI improvement in the OPCABG group not only for LAD territories but also for non-LAD regions, associated with a reduction in the negative left ventricular ischemic remodeling, compared to patients discharged in optimal medical therapy. Global ΔWMSI was negative in OPCAB group (-3.4 ± 2.8%) and positive in the OMT group (5.9 ± 3.1%), indicating a better wall motion score for OPCAB patients. Surprisingly, regional WMSI improved also in non-grafted territories in the OPCAB group with a delta value of -3.7 ± 5.3% for left circumflex artery (LCX) area and -3.5 ± 5.4% for right coronary artery (RCA) area. Conclusions In patients with multivessel coronary artery disease, LIMA-to-LAD grafting is associated with an improvement in the WMSI involving also the surrounding non-LAD ungrafted segments and with the attenuation of negative global and regional ischemic ventricular remodelling.