Psychiatric staff are faced with multiple forms of hostility, aggression, and assault at work, collectively referred to as workplace violence, which typically is activated by patients but can also come from coworkers and supervisors. Whether workplace violence adversely affects staff well-being may be related not only to its presence, but also to an individual’s stress reactivity. At a large public psychiatric hospital, an online survey was completed by 323 clinical care staff, of whom 69.5% had experienced physical assault in the previous 12 months. Staff well-being (depression, anger, and physical health) and staff safety concerns were adversely affected by conflicts with other staff members and by individual reactivity to social conflict and to assault. To improve staff well-being, in addition to safety protocols, interventions should target staff relationships, personal health maintenance practices, and individual coping skills for dealing with adverse workplace experiences.