Introduction: Sex‑related differences in outcomes after left main coronary artery (LMCA) percutaneous coronary intervention (PCI) remain incompletely understood, particularly in real‑world settings.

Objectives: This study evaluated the impact of sex assigned at birth on long‑term clinical outcomes after LMCA PCI in the largest single‑center registry in Poland.

Patients and methods: We retrospectively analyzed 998 patients who underwent LMCA PCI between 2007 and 2022. The endpoint was 5‑year all‑cause mortality. Survival analyses were performed in the overall cohort and after propensity score matching (PSM) and inverse probability of treatment weighting (IPTW).

Results: The final cohort included 814 patients, of whom 228 (28%) were women. In the overall population, there was no difference in 5‑year mortality between men and women (HR 1.31, 95% CI 0.99–1.73; P = 0.06). PSM resulted in 471 pairs, and IPTW generated a weighted cohort of 469 patients (131 [28%] women). After PSM, men had significantly higher mortality (HR 1.64, 95% CI 1.28–2.11; P <0.001), consistent with IPTW analysis (HR 1.71, 95% CI 1.04–2.83; P = 0.04). Exploratory subgroup analyses demonstrated higher mortality among men with heart failure (HR 2.25, 95% CI 1.66–3.04; P = 0.002), undergoing rotational atherectomy (HR 4.15, 95% CI 2.25–7.65; P <0.001), and treated for ≥2 lesions (HR 2.02, 95% CI 1.44–2.83; P <0.001).

Conclusions: Men experienced worse long‑term survival than women after adjustment for clinical and procedural confounders. Mortality risk was higher among men with heart failure, multivessel disease, and those undergoing rotational atherectomy, highlighting the importance of considering sex‑based differences in LMCA management.