Objectives Workplace violence is a concerning issue. Healthcare workers represent a significant portion of the victims, especially those who work in the emergency department (ED). The objective of this study was to examine ED workplace violence and staff perceptions of physical safety. Methods Data were obtained from the National Emergency Department Safety Study (NEDSS), which surveyed staff across 69 U.S. EDs including physicians, residents, nurses, nurse practitioners, and physician assistants. The authors also conducted surveys of key informants (one from each site) including ED chairs, medical directors, nurse managers, and administrators. The main outcome measures included physical attacks against staff, frequency of guns or knives in the ED, and staff perceptions of physical safety. Results A total of 5,695 staff surveys were distributed, and 3,518 surveys from 65 sites were included in the final analysis. One-fourth of surveyed ED staff reported feeling safe sometimes, rarely, or never. Key informants at the sampled EDs reported a total of 3,461 physical attacks (median of 11 attacks per ED) over the 5-year period. Key informants at 20% of EDs reported that guns or knives were brought to the ED on a daily or weekly basis. In multivariate analysis, nurses were less likely to feel safe “most of the time” or “always” when compared to other surveyed staff. Conclusions This study showed that violence and weapons in the ED are common, and nurses were less likely to feel safe than other ED staff.