Background: Percutaneous coronary intervention (PCI) is a core strategy in the management of coronary artery disease. Mortality after PCI is influenced by patient risk, lesion complexity, system factors, and operator-related variables. Among these, operator experience—often measured by annual PCI volume or cumulative career cases—is increasingly recognized as a modifiable determinant of outcomes.Objective: To examine the association between operator experience and in-hospital mortality after PCI, and to explore whether this association persists after adjustment for patient risk profile and procedural complexity.Methods: We conducted a multicenter observational study including 8 PCI-capable hospitals across South Asia from January 2020 to December 2023. A total of 9,500 consecutive PCI procedures (elective, urgent, and primary PCI) performed by 45 operators were analyzed. Operators were stratified into three groups based on annual PCI volume and years of independent practice: low-experience (≤75 PCI/year or <3 years), intermediate (76–150 PCI/year and 3–7 years), and high-experience (>150 PCI/year or >7 years). Primary outcome was in-hospital all-cause mortality. Secondary outcomes included major adverse cardiovascular events (MACE: death, MI, stroke, urgent CABG) and procedural complications (coronary perforation, major bleeding, stent thrombosis). Multivariable logistic regression and hierarchical modeling (patients nested within operators) were used.Results: Overall in-hospital mortality was 2.3%. Mortality was highest in the low-experience group (3.4%), followed by intermediate (2.2%) and high-experience operators (1.7%; p < .001). After adjustment for age, comorbidities, left ventricular function, lesion complexity, and urgency of procedure, low-experience operators had significantly higher odds of in-hospital mortality compared with high-experience operators (adjusted OR 1.78, 95% CI 1.29–2.46). The difference was most pronounced in high-risk subgroups (STEMI with shock, left main PCI, multivessel disease).Conclusion: Operator experience is independently associated with PCI mortality, particularly in complex or high-risk cases. Policies that support minimum volume standards, structured mentorship, and careful allocation of high-risk procedures to seasoned operators may help reduce PCI-related mortality.