Background <p>There is a paucity of data regarding early- and long-term outcomes of coronary artery bypass grafting (CABG) in left main coronary artery disease (LMCAD) in comparison to non-LMCAD patients.</p> Methods <p>From November 2014 to December 2022, 2605 consecutive patients underwent isolated CABG procedure in our institution. Six hundred and twenty-five patients (24%) had LMCAD. Retrospective data collection from case files was combined with prospective patient follow-up. Since the baseline characteristics of the two groups were not similar, we used propensity matching with a single hidden layer neural network using a one-to-one nearest neighbor to generate matched 1:1 pairs. We compared the outcomes of 556 LMCAD patients with 556 non-LMCAD patients. We compared the 30-day outcomes, overall long-term survival, event-free survival, major adverse cardiovascular and cerebral event (MACCE) survival, and hazard of cardiovascular deaths.</p> Results <p>The median follow-up period was 4.9&#xa0;years. The 30-day outcomes were similar in the matched cohort. However, overall survival was diminished in LMCAD patients. (The mean survival time in the non-LMCAD group was 3199.99 ± 38.96&#xa0;days and in the LMCAD group, it was 3085.60 ± 47.34 (<i>p</i>-value 0.025).) LMCAD patients also had a higher hazard of cardiovascular death (<i>p</i>-value of 0.037). But the event-free survival and MACCE-free survival were similar in both groups. Multivariate Cox regression analysis in the matched cohort showed that LMCAD was an independent predictor of long-term mortality (hazard ratio (HR) 1.74; confidence interval (CI) 1.2–2.51).</p> Conclusion <p>Our study showed that LMCAD patients had increased cardiovascular mortality and inferior overall survival compared to non-LMCAD patients in a propensity-matched sample. Further multi-center studies or analyses of large registry data are needed to confirm the findings of this study.</p> Graphical Abstract <p></p>