Background <p>Patients with coronary artery disease (CAD) with low left ventricular ejection fraction (LLVEF) (LVEF ≤ 35%) are not considered suitable for minimally invasive cardiac surgery - off-pump coronary artery bypass grafting (MICS OPCABG) due to poor cardiac function reserve.</p> Methods <p>We retrospectively analyzed 38 consecutive CAD patients with LLVEF who underwent MICS OPCABG from January 2022 to December 2024. We collected perioperative and follow-up data to evaluate the feasibility of this procedure as well as mid-term prognosis.</p> Results <p>The mean age of the study patients was 65.5 ± 8.8 years, and the preoperative LVEF was 29.2 ± 4.0%. 15 patients (39.5%) had diabetes mellitus, 6 patients (15.8%) had chronic kidney disease (CKD). Mitral regurgitation (MR) was combined in 36 cases (94.7%). The in-hospital mortality rate was 7.89% (3/38). LVEF gradually improved: it increased to 42.3 ± 6.8% at postoperative 3 months (<i>P</i> &lt; 0.001vs baseline), 48.1 ± 7.2% at postoperative 12 months (<i>P</i> &lt; 0.001vs baseline), and stabilized at 49.5 ± 6.5% at postoperative 24 months. Mitral regurgitant area (MRA) was significantly reduced: it decreased to 5.1 ± 2.3&#xa0;cm² at postoperative 3 months (<i>P</i> &lt; 0.001vs baseline), and stabilized at 4.9 ± 2.3&#xa0;cm² at postoperative 12 months (<i>P</i> &lt; 0.001vs baseline), and 4.8 ± 2.1&#xa0;cm² at postoperative 24 months. The 3-year all-cause cumulative mortality rate was 15.29%. Multivariable Cox regression showed that preoperative LVEF ≤ 25% (HR = 3.29, 95%CI 1.98–9.83, <i>P</i> = 0.022), combined preoperative CKD (HR = 2.77, 95%CI 1.08–6.65, <i>P</i> = 0.026) and LIMA-LAD blood flow ≤ 15&#xa0;ml/min (HR = 1.97, 95%CI 1.31–3.93, <i>P</i> = 0.041) were independent predictors of 3-year mortality. In addition, the 3-year all-cause cumulative graft patency rate was 87.23%.</p> Conclusions <p>MICS OPCABG provides a combined improvement in LVEF and MR and a favorable graft patency rate for CAD patients with LLVEF and ischemic MR.</p>