BACKGROUND: Understanding how and when a new evidence-based clinical intervention becomes standard practice is crucial to ensure that healthcare is delivered in alignment with the most up-to-date knowledge. However, rigorous methods are needed to determine when a new clinical practice becomes normalized to the standard of care. To address this gap, this study qualitatively explores how, when, and why a clinical practice change becomes normalized within healthcare organizations. METHODS: We used purposive sampling to recruit clinical leaders who worked in implementation science across diverse health contexts. Enrolled participants completed semi-structured interviews. Qualitative data analysis was guided by a modified version of the Normalization Process Theory (NPT) framework to identify salient themes. Identified normalization strategies were mapped to the Expert Recommendations for Implementation Change (ERIC) project. RESULTS: A total of 17 individuals were interviewed. Participants described four key signals for identifying when a novel clinical practice becomes the new normal: 1) integration into existing workflows; 2) scaling across the entire organizational unit; 3) staff buy-in and ownership; and 4) sustainment without ongoing monitoring. Participants identified salient strategies to normalize new clinical interventions: 1) taking a patient approach; 2) gaining staff buy-in and ownership; and 3) conducting ongoing measurement of progress towards normalization. CONCLUSIONS: The results offer valuable insight into the indicators that signify when a novel clinical practice becomes normalized, and the strategies employed to facilitate this transition. These findings can inform future research to develop instruments that implementation leaders can use to systematically measure the clinical change process.