Patient safety is one of the most important issues in healthcare. High-risk percutaneous coronary interventions (HR-PCIs) offer well-established treatment options for patients with complex coronary artery disease and multiple comorbidities. Whether process standardization using standard operating procedure (SOP) management and checklists improves HR-PCI is still unknown. This retrospective study analyzed procedural characteristics, in-hospital outcomes, and length of hospital stay in patients who received HR-PCI in a German heart center 12 months before the introduction of process standardization using SOP management-the SOP (-) group-and after the introduction of process standardization using SOP management-the SOP (+) group. A total of 192 patients were included, with 77 patients in the SOP (-) group and 115 patients in the SOP (+) group. The mean age in the SOP (-) group was 72.0 ± 10.2 years and 81.8% were male; mean age in the SOP (+) group was 75.2 ± 10.4 years and 68.7% were male. Acute kidney events were significantly lower in the SOP (+) group than in the SOP (-) group (7.0% vs 10.4%; P=.04). Bleeding was the most common adverse event and significantly lower in the SOP (+) group than in the SOP (-) group (13.1% vs 31.2%, respectively; P<.01). There were trends toward shorter length of hospital stay in the SOP (+) group compared with the SOP (-) group (9.3 ± 6.4 days vs 10.9 ± 7.3 days, respectively; P=.10) and days of hospital stay in the intensive care unit (3.7 ± 4.0 days vs 4.7 ± 4.3 days; P=.07). SOP management was independently associated with shorter length of hospital stay in multivariate regression analysis. This retrospective study shows significantly better quality of care measures after the introduction of process standardization techniques using SOP management in HRPCIs, with a lower risk of adverse outcomes and shorter length of hospital stay.