© 2021 Wiley Periodicals LLCAim: Chest computed tomography (CT) imaging plays a diagnostic and prognostic role in Coronavirus disease 2019 (COVID-19) patients. This study aimed to investigate and compare predictive capacity of main pulmonary artery diameter (MPA), ascending aorta diameter (AAo), and MPA-to-AAo ratio to determine in-hospital mortality in COVID-19 patients. Materials and methods: This retrospective study included 255 hospitalized severe or critical COVID-19 patients. MPA was measured at the level of pulmonary artery bifurcation perpendicular to the direction of the vessel through transverse axial images and AAo was measured by using the same CT slice at its maximal diameter. MPA-to-AAo ratio was calculated by division of MPA to AAo. Results: Multivariate logistic regression model yielded MPA ≥29.15 mm (OR: 4.95, 95% CI: 2.01–12.2, p = 0.001), MPA (OR: 1.28, 95% CI: 1.13–1.46, p < 0.001), AAo (OR:.90, 95% CI:.81–.99, p = 0.040), and MPA-to-AAo ratio ≥.82 (OR: 4.67, 95% CI: 1.86–11.7, p = 0.001) as independent predictors of in-hospital mortality. Time-dependent multivariate Cox-proportion regression model demonstrated MPA ≥29.15 mm (HR: 1.96, 95% CI: 1.03–3.90, p = 0.047) and MPA (HR: 1.08, 95% CI: 1.01–1.17, p = 0.048) as independent predictors of in-hospital mortality, whereas AAo and MPA-to-AAo ratio did not reach statistical significance. Conclusion: Pulmonary artery enlargement strongly predicts in-hospital mortality in hospitalized COVID-19 patients. MPA, which can be calculated easily from chest CT imaging, can be beneficial in the prognostication of these patients.