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Background: Hospital preparedness for accidents like fires is essential because fire outbreaks in healthcare settings can occur anytime and require quick responses. Therefore, this study assessed the knowledge of fire safety and emergency preparedness among healthcare workers, as well as the predictors of knowledge of fire safety and emergency preparedness among healthcare workers. Methods: An institutional-based descriptive cross-sectional online survey was employed to assess knowledge of fire safety and emergency preparedness among 257 healthcare workers from three hospitals in the Kunene region. Both descriptive and inferential statistics were carried out using STATA version 18. Frequencies and percentages were used in the descriptive statistics and Pearson's chi square test, correlation analysis and logistic regression were adapted for the inferential statistics. The statistical significance level was set at p-value ≤ 0.05 at 95% confidence interval. Results: The study observed that 72.76% of the healthcare workers lack adequate level of knowledge concerning emergency preparedness while 73.15% of healthcare workers lack sufficient knowledge regarding fire safety. The findings further indicated that there is a strong relationship (r = 0.992) between fire safety knowledge and emergency preparedness among healthcare workers. The study findings also shows that gender (< 0.0001), and place of work (< 0.0001) were associated with knowledge of fire safety and emergency preparedness. Male participants were more likely to have adequate knowledge of fire safety (aOR: 3.74; 95%CI: 2.016 – 6.950) and emergency preparedness (aOR: 3.64; 95%CI: 1.956 – 6.756) compared to females. The healthcare workers at Khorixas district hospital had lower odds (aOR: 0.354; 95%CI: 0.173 – 0.724) of having adequate knowledge of emergency preparedness compared to those working at the Opuwo hospital. Conclusion: The majority of the studied healthcare professionals did not have adequate knowledge regarding emergency preparedness. Addressing the gaps in fire safety knowledge and preparedness among healthcare workers is critical to ensuring a safe healthcare environment. By implementing targeted training programs and safety protocols, healthcare facilities can significantly enhance their emergency response capabilities, ultimately safeguarding both staff and patients. [ABSTRACT FROM AUTHOR]