Introduction: Anti-Indigenous racism within healthcare has been well-documented globally. In response, there have been calls for the expansion of Indigenous cultural safety (ICS) education to all healthcare staff. Given limited evidence on the impacts of ICS education within acute healthcare settings, this study sought to evaluate changes in Emergency Department (ED) staff’s understanding and application of ICS within their health care practice. Methods: Employing a one-group, pre- and post-test study design, the Cultural Capability Measurement Tool (CCMT), and other standalone questions on cultural competence, were administered to ED staff at a large urban hospital in Vancouver, Canada both before and after the completion of a new, introductory, and in-person ICS education program. Paired t-tests examined changes in CCMT scores, and Wilcoxon rank sign test was used to assess changes in standalone questions. Results: A total 66 ED staff complete a pre- and post-test survey. Statistically significant improvements were seen in three of four of the domains of the CCMT, including in respect (p=0.015), communication (p<0.001), and safety and quality (p=0.005), though no statistically significant improvements were observed in the reflection and advocacy domain (p=0.189). Similarly, statistically significant improvements were observed across other measures of cultural competency in relation to general knowledge, workplace applications of ICS, and how to meaningfully engage with Indigenous patients (all p<0.05). Conclusions: Findings indicate that expanding ICS education in healthcare is critical to reducing anti-Indigenous racism and improving Indigenous Peoples’ trust in the healthcare system. This may include providing regular, routine ICS education opportunities for healthcare staff and incorporating ICS teachings into medical education curriculum. Future research comparing changes in cultural competency between an intervention and control group of healthcare staff is recommended and would be valuable, as well as research into Indigenous Peoples’ experiences before and after the implementation of a healthcare-specific ICS education program.