Purpose: Identifying effective approaches to achieve safe and inclusive environments is a priority for academic medical centers and health care systems. However, mistreatment of health care providers (HCPs) is common and is associated with burnout 1 and lower quality patient care. 2 Unfortunately, mistreatment of HCPs by patients and their family members is underreported. 3 Furthermore, data on effective methods to mitigate mistreatment are lacking. We investigated the prevalence of mistreatment of HCPs by patients and family members in an academic, tertiary care children’s hospital. We hypothesized that an organizational strategy that uses patient quality and safety infrastructure, consisting of training, incident reporting, and response protocol, would increase HCP knowledge of and self-efficacy in addressing and reporting mistreatment. Design and Methods: In this single-center, serial cross-sectional study, we sent anonymous surveys to HCPs before and at least 5 months after intervention, consisting of training, safety incident reporting, and response protocol, to assess knowledge, self-efficacy, and experiences of mistreatment at the Yale New Haven Children’s Hospital 2018–2019. Training included ERASE 4 and “Ouch! That Stereotype Hurts” 5 sessions. We modified the hospital’s electronic safety incident reporting software to track mistreatment events that were reviewed daily and acted upon by quality and safety leadership. We developed a response algorithm that provided guidance for handling mistreatment in real time and reporting mistreatment events. Multivariable logistic regression was used to examine the effect of intervention on the outcomes of interest and whether this association was moderated by staff role. Results: A total of 309 baseline surveys were completed by 72 faculty, 191 nurses, and 46 residents, representing 39.1%, 27.1%, and 59.7%, respectively, of eligible HCPs. Verbal threats from patients/family were reported by 69.5% of HCPs. Offensive behavior was most commonly based on age (85, 28.5%), gender (85, 28.5%), ethnicity or race (55, 18.5%), and appearance (43, 14.6%) but varied by role. HCPs who received training had higher odds of reporting knowledge of mistreatment policies (OR 2.7; 95% CI, 1.38–5.32), a standardized approach to address mistreatment (OR 4.43; 95% CI, 2.03–9.67), and intervening effectively when mistreated (OR 1.93; 95% CI, 0.93–4.01) or when witnessing mistreatment (OR 2.39; 95% CI, 0.99–5.78]). Incident reporting of mistreatment increased 3-fold after intervention. Discussion: We found that the majority of pediatric HCPs in our study reported experiencing mistreatment by patients and their family members, which is concerning given the potential adverse consequences on HCPs and patient care. We were able to demonstrate that training was associated with increased odds of HCPs reporting knowledge and self-efficacy at least 5 months later, supporting long-term benefits. That training was associated with increased odds of experiencing offensive behaviors, which is likely due to enhanced awareness, as it was covered in the curriculum. While it is possible that the increase in incident reports of mistreatment reflects an increase in the number of events, our results suggest that it is more likely due to increased awareness of mistreatment and enhanced safety culture that promotes event reporting. Significance: This is the first report of an effective organizational approach to address mistreatment of HCPs by patients and family members. It capitalizes on existing patient safety culture and infrastructure and can be adopted by other institutions to combat all forms of mistreatment, including racism.