Background: Nonsurgical centers (NSC) contribute significantly to the capacity of overall percutaneous coronary intervention (PCI) in the United Kingdom. Although previous studies have demonstrated similar PCI outcomes in surgical centers (SC) versus NSC, it is unknown whether this applies to more complex procedures such as left main stem (LMS) PCI. We compared patient characteristics and outcomes of LMS PCI performed across SC and NSC in England and Wales. Methods: A retrospective analysis of procedures between January 2006 and March 2020 was performed using the British Cardiovascular Intervention Society database and stratified according to the surgical status of the center. The primary outcomes assessed were in-hospital major adverse cardiovascular and cerebrovascular events, all-cause mortality, and Bleeding Academic Research Consortium stage 3 to 5 bleeding. Results: Forty thousand seven hundred forty-four patients underwent LMS PCI during the period, of which 13 922 (34.2%) had their procedure performed at an NSC. The proportion of LMS PCI performed in NSC increased >2-fold (15.9% in 2006 to 36.7% in 2020). There was no association between surgical cover location and in-hospital mortality (odds ratio, 0.92 [95% CI, 0.69–1.22]), in-hospital major adverse cardiovascular and cerebrovascular events (odds ratio, 1.00 [95% CI, 0.79–1.25]), or emergency coronary artery bypass graft surgery (odds ratio, 1.00 [95% CI, 0.95–1.06]). NSC had lower Bleeding Academic Research Consortium 3 to 5 bleeding complications (odds ratio, 0.53 [95% CI, 0.34–0.82]). Conclusions: There has been an increase in LMS PCI volumes at NSC, particularly elective LMS PCI. LMS PCI performed at NSC was not associated with increased mortality, in-hospital major adverse cardiovascular and cerebrovascular events, or emergency coronary artery bypass graft surgery, despite higher disease complexity.