This study aimed to assess the prevalence and associated factors of post-traumatic stress disorder among health professionals working in South Gondar Zone hospitals in the era of the COVID-19 pandemic, Amhara Ethiopia 2020. Institutional based cross-sectional study design was conducted. A total of 396 respondents completed the questionnaire and were included in the analysis. A previously adapted self-administered pretested standard questionnaire, Impact of Event Scale-Revised (IES-R-22) was used to measure post-traumatic stress disorder. Data was entered into Epi data version 4.4.2 then exported to SPSS version 24 for analysis. Descriptive and analytical statistical procedures, bivariate, and multivariate binary logistic regressions with odds ratios and 95% confidence interval were employed. The level of significance of association was determined at a p-value < 0.05. The prevalence of post-traumatic stress disorder among health care providers in this study was 55.1% (95% CI: 50.3, 59.6). Lack of standardized PPE supply (AOR = 2.5 7,95CI;1.37,4.85), respondents age > 40 years (AOR = 3.95, 95CI; 1.74, 8.98), having medical illness (AOR = 4.65, 95CI;1.65,13.12), perceived stigma (AOR = 1.97, 95CI;1.01, 3.85), history of mental illness(AOR = 8.08,95IC;2.18,29.98) and having poor social support (AOR = 4.41,95CI;2.65,7.3) were significantly associated with post-traumatic stress disorder at p-value < 0.05. Conversely, being a physician (AOR = 0.15, 95CI; 0.04, 0.56) was less affected by PTSD. The prevalence of post-traumatic stress disorder among health care providers in this study was high. Adequate and standardized PPE supply, giving especial emphasis to those care providers with medical illness, history of mental illness, and having poor social support, creating awareness in the community to avoid the stigma faced by health care providers who treat COVID patients is recommended.