Rising incidents of violence and mistreatment of healthcare workers by patients and visitors have been reported. U.S. healthcare workers are five times more likely to experience nonfatal workplace violence (WPV) than workers in any other profession. However, less is known about the national trends in the incidence of violence and mistreatment in healthcare. The specific organizational and individual-level factors that relate to stress arising from these occurrences specifically by patients and family members are also not fully understood. The goals of this study were to examine national trends of violence toward healthcare workers, understand which populations are most vulnerable to stress from violence and mistreatment, and explore organizational factors that are related to these occurrences. Data were collected from three sources: (1) The Bureau of Labor Statistics Intentional Injury by Another Person data for the period 2011-2020, (2) data from a large national workers' compensation claim services provider for the period 2018-2022, and (3) results from a survey distributed at a large medical center in June and July 2022. Data were represented graphically and analyzed using multivariate regression and dominance analysis to identify specific predictors of WPV and mistreatment among healthcare workers. Of the total surveyed sample, 23.7% of participants reported mistreatment from patients or visitors as a major stressor and 14.6% reported WPV from patients or visitors as a major stressor. Stress from mistreatment and WPV was most frequently reported by nurses, employees aged 18 to 24 years other than nurses, those who identified as White, and those who identified as female or a gender minority. The emergency room (ER) showed the highest percentages of stress from mistreatment (61.8%) and violence (55.9%) from patients or visitors. The top predictors of stress from WPV and mistreatment by patients or visitors among healthcare workers ranked high to low were working in the ER, working as a nurse, a lack of necessary supplies or equipment, patient or visitor attitudes or beliefs about COVID-19, and working in a hospital-based unit. In addition to protecting employees as a moral imperative, preventing WPV is critical for organizational performance. Employee productivity is estimated to decrease up to 50% in the 6 to 18 weeks following an incident of violence, while turnover can increase 30% to 40%. An effective WPV prevention plan and a proactive approach to supporting the physical and mental health conditions that may result from WPV can mitigate the potential costs and exposures from these incidents. Organizations must also set clear expectations of behavior with patients and visitors by refusing to tolerate violence and mistreatment of caregivers. The impact of WPV can remain present and active for up to 8 years following an incident. Policy-level interventions are also needed. Currently, there are no federal protections for healthcare workers related to violence, though some states have made it a felony to abuse healthcare workers.