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Background: Health Care Workers (HCWs) in conflict zones face high levels of violence while also playing a crucial role in assisting the population in distress. For more than two decades, the eastern provinces of the Democratic Republic of the Congo (DRC), have been wracked by conflict. This study aims to describe the state of violence against HCWs and the potential prevention mechanisms in eastern DRC. Methods: In North and South Kivu, between February 5 and 21, 2021, we conducted a mixed cross-sectional convergent study in health facilities (health centers and hospitals). An anonymized self-administered questionnaire was sent to HCWs about their experience of violence in the 12 months prior to the study. In-depth individual interviews with HCWs, present on the day of the investigation, were also done to explore their experience of violence. A descriptive analysis of the quantitative data and a thematic analysis of the qualitative data was carried out. Results: Of a total of 590 participants, 276 (45.9%) reported having experienced violence in the 12 months before the study. In North Kivu, aggressors were more frequently the patients (43.7% vs. 26.5%) and armed group members (14.3% vs. 7.9%) than in South Kivu. Most respondents (93.5%) reported verbal aggression (insults, intimidation, death threats). Other forms of physical aggression including with bare hands (11.2%), firearm (1.81%), and stabbing (4.7%). Only nearly one-tenth of the attacks were officially reported, and among those reported a higher proportion of sanctions was observed in South Kivu (8.5%) than in North Kivu (2.4%). The mechanisms proposed to prevent violence against HCWs were community initiatives and actions to strength the health system. Conclusions: In Eastern DRC, HCWs face multiple and severe forms of aggression from a variety of individuals. The effects of such levels violence on HCWs and the communities they served could be devastating on the already pressured health system. Policy framework that defines the roles and responsibilities for the protection of HCWs and for the development and implementation of preparedness measures such as training on management of violence are possible solutions to this problem. [ABSTRACT FROM AUTHOR]