BACKGROUND: The adoption of multi-arterial grafting (MAG) remains limited in real-world coronary artery bypass grafting (CABG) practice. This study aimed to identify subsets of patients most likely to benefit clinically from MAG, and to explore potential effect modifiers of its treatment benefit, including renal function. METHODS: This retrospective cohort study analyzed 3,244 isolated CABG patients from a prospectively maintained institutional registry (2006-2020). Patients were categorized into MAG (n = 1,868) and single-arterial grafting (SAG; n = 1,376) groups. Inverse probability treatment weighting was applied to adjust for baseline differences, and Cox proportional hazards models evaluated overall survival. Subgroup analyses assessed interactions between treatment effects and patient characteristics, particularly estimated glomerular filtration rate (eGFR). RESULTS: Over a median follow-up of 7.1 years, MAG demonstrated significantly higher overall survival compared to SAG (P < 0.001). After adjustment, MAG still provided a significant survival advantage (adjusted hazard ratio [aHR], 0.77; 95% confidence interval [CI], 0.65-0.92; P = 0.005). MAG consistently showed favorable outcomes across most patient subgroups regardless of age, sex, diabetes, peripheral arterial disease, smoking status, or left ventricular function. However, renal function significantly modified this effect (interaction P = 0.005); MAG conferred significant survival benefits in patients with eGFR ≥ 51 mL/min/1.73 m² (aHR, 0.51; 95% CI, 0.66-0.99; P = 0.044), whereas no difference was observed in those with eGFR < 51 (aHR, 1.00; 95% CI, 0.74-1.36; P = 0.999). CONCLUSION: MAG offers significant survival advantages for CABG patients with relatively preserved renal function (eGFR ≥ 51). Renal function should thus be considered when selecting arterial grafting strategies to optimize patient outcomes.