Percutaneous coronary intervention (PCI) has evolved dramatically, along with patient complexity. We studied trends in in-hospital mortality with changes in patient complexity over the last decade stratified by clinical presentation. The study population included all patients presenting to the cardiac catheterization lab between January 2009 and July 2018. Expected in-hospital mortality was calculated using the National Cardiovascular Data Registry CathPCI risk scoring system. Yearly mean in-hospital mortality rates (%) were plotted and smoothed by weighted least squares regression for each presentation: ST-elevation myocardial infarction (STEMI), non–ST-elevation acute coronary syndrome (NSTE-ACS), and stable ischemic coronary artery disease (SI CAD). The overall cohort included 13,732 patients who underwent PCI during the study period, of whom 2,142 were for STEMI, 2,836 for NSTE-ACS, and 8,754 for SI CAD. Indications for PCI have changed over time, with more PCIs being performed for NSTE-ACS and STEMI than for SI CAD. NSTE-ACS and STEMI patients had a steady decrease in in-hospital mortality over time compared with SI CAD patients. Overall observed mortality continues to decrease in NSTE-ACS patients, with reduction in the observed mortality rate within the STEMI population to below expected since 2013. Patient complexity has not changed significantly. These results may be attributed to improved patient selection coupled with optimal pharmacotherapy with more robust therapies during procedure and hospitalization.