Background: During infectious disease pandemic, patients with chronic medical diseases were at increased risk of mental health problems. Therefore, the study assessed posttraumatic stress symptoms amid the COVID-19 pandemic among patients with chronic medical diseases. Methods: A facility-based cross-sectional study was conducted from August 1- 20, 2020. Systematic random sampling was used to select 422 patients with chronic medical diseases (diabetes, hypertension, and HIV). Impact of the event scale revised was used to assess posttraumatic stress symptoms. Data were analyzed by using SPSS version 23. Multivariable logistic regression analysis with 95% CI and odds ratio were fitted to declare the significantly associated variables at P value < 0.05. Results: 230 (54.5%) of the participants were reported to have posttraumatic stress symptoms. Being female, AOR=3.65 (95% CI 2.08, 6.40), Duration of illness greater than five-year AOR=3.12 (95% CI 1.73, 5.65), presence of anxiety AOR=6.52 (95% CI 3.71, 11.47), Age ≥55 year AOR=3.45 (95% CI 1.49, 7.98), diagnosis of diabetes AOR=7.49 (95% CI 3.65, 15.35), hypertension AOR=4.45 (95% CI 2.29, 8.64) and poor social support AOR=2.16 (95% CI 1.26, 3.68) were observed to have significant association with posttraumatic stress symptoms. Conclusion: Significant posttraumatic stress symptoms were reported by more than half of the patients with chronic medical diseases. This was of considerable concern indicating a significant impact of COVID-19 pandemic on this group, which seeks attention for early psychological intervention.