Objective: Emergency preparedness and response operations for all types of catastrophes rely heavily on healthcare facilities and their staff. On the other hand, hospital employees suffer significant gaps in emergency preparedness knowledge and skills when it comes to treating mass casualties. The objective of this study was to assess the nurses’ and physicians’ familiarity with emergency preparedness and identify the associated factors. Methods: A facility-based cross-sectional survey was conducted by census utilizing a self-administered questionnaire among all nurses and physicians working in emergency departments in East Gojjam zone public hospitals. The collected data were entered into Epi-data version 4.2 and exported to SPSS 25.0 for further analysis. Frequency, mean, and standard deviation were computed to describe individual and other characteristics of the sample. A simple and multiple linear regression model was fitted to identify factors associated with familiarity with emergency preparedness. An unstandardized adjusted beta ( β) coefficient with a 95 % confidence level was used to report the result of the association at a p-value of 0.05 statistical significance. Results: In this study, a total of 237 individuals completed the questionnaire, yielding a response rate of 94 %. The mean score of familiarity with emergency preparedness was 106.1 ± 31.8 (95% CI: 102, 110.1), with approximately 52.3 % scoring higher than the mean score. Self-regulation (B = 3.8, 95% CI: 2.6, 5), health care climate (B = 1.4, 95% CI: 0.4, 2.43) and participation in actual major disaster event (B = 15.5, 95% CI: 7.8, 23.2) were significant predictors of familiarity. Conclusion: According to the findings of this study, nurses’ and physicians’ expertise in emergency and disaster preparedness is inadequate. Previous engagement in actual disaster events, self-regulation, and the healthcare climate were significant predictors of familiarity. As a result, the responsible stakeholders should develop strategy to enhance self-regulation (motivation), job satisfaction of emergency department employees, and drills and hands-on training in mass casualty management.