Background: Post-Traumatic Stress Disorder (PTSD) is chronic in a significant proportion of war survivors many years after the war when untreated, results in functional impairments and decreased health-related quality of life. Therefore, knowing the prevalence helps to plan mental health and psychosocial interventions. However, there was limited research in adult population residents in war-affected area in Ethiopia specifically in Dessie Town. Objectives: This study aimed to assess the prevalence of Post-Traumatic Stress Disorder and its associated factors among residents in war-affected area, Dessie Town, North East, Ethiopia, 2022. Methods: Community-based cross-sectional study was conducted among adult residents in war affected area, Dessie Town. A total of 615 individuals were selected by systematic random sampling method. Data was collected using structured questionnaires. PTSD was assessed using Post-Traumatic Stress Disorder Checklist Civilian Version. Standard tools were used to measure the associated factors. Coded data was entered into Epi data version 4.6 then exported to statistical package for social science version 25 for analysis. To analyze the result bivariable and multivariable logistic regressions with odds ratios and 95% confidence interval and at p<0.05 was employed. Results: This study had 600 participants and a 97.6% response rate. The prevalence of PTSD in this study was 34.5 % (95% CI; 31, 38). In multivariable regression the factors associated with PTSD were female sex (AOR: 1.86, CI; 1.19, 2.92), divorced/widowed (AOR: 2.03, CI; 1.16, 3.55), can’t read and write (AOR: 2.91, CI; 1.23, 6.87), primary schooling (AOR: 3.28, CI; 1.63, 6.61), secondary schooling (AOR: 2.43, CI; 1.20, 4.92), diploma (AOR: 2.66, CI; 1.36, 5.19), depression (AOR: 1.94, CI; 1.25, 3.0), suicidal behavior (AOR: 1.8, CI; 1.04, 3.1), Ill health without medical care (AOR: 2.66, CI; 1.24, 5.69), forced separation from family (AOR: 2.04, CI; 1.22, 3.43), and stressful life event (AOR: 1.69, CI; 1.08, 2.63). Conclusion and recommendation: The prevalence of PTSD was found to be high among residents in war-affected area, Dessie Town. Female sex, being divorced(widowed), educational status, depression, suicidal behavior, ill health without medical care, forced separation and stressful life was its determinant factors. Therefore, Dessie Town health office need to screen and provide treatment for residents suffering from PTSD and depression. Key words: - Dessie Town, Post-Traumatic Stress Disorder, Residents, War, War