Percutaneous coronary intervention (PCI) is an established alternative to coronary artery bypass grafting for the treatment of select patients with unprotected left main (LM) coronary artery disease (CAD). This study evaluates the safety and clinical impact of treating additional coronary arteries during LM-PCI. Consecutive patients undergoing PCI with drug-eluting stents for unprotected LM-CAD between 2010 and 2021 at The Mount Sinai Hospital, New York, USA were eligible for inclusion. Patients were stratified based on whether they underwent treatment of the LM complex alone or had concomitant PCI to an additional vessel outside the LM complex. The primary outcome was major adverse cardiovascular events (MACE), a composite of death, myocardial infarction, or stroke, at 1 year following PCI. Among 869 consecutive patients (mean age 70.9, 33.0% female, 27.9 mean SYNTAX score) undergoing LM-PCI, 479 (55.1%) underwent treatment of the LM complex alone, and 390 (44.9%) had concomitant PCI of an additional non-LM vessel. Compared with LM complex PCI only, there were no significant differences in the rate of MACE at 1 year [HR 12.0% vs 13.3%; HR: 0.95; 95% CI (0.62-1.44), p = 0.797], even after adjustment for potential confounders [HR 12.0% vs 13.3%; HR: 0.87; 95% CI (0.56-1.36), p = 0.550]. In conclusion, in a large, real-world cohort of patients undergoing unprotected LM-PCI, treatment of an additional non-LM vessel did not increase the risk of MACE at 1 year compared to LM complex PCI alone. (c) 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.