OBJECTIVE: To evaluate whether the initial chest X-ray (CXR) severity assessed by an AI system may have prognostic utility in patients with COVID-19. METHODS: This retrospective single-center study included adult patients presenting to the emergency department (ED) between February 25 and April 9, 2020, with SARS-CoV-2 infection confirmed on real-time reverse transcriptase polymerase chain reaction (RT-PCR). Initial CXRs obtained on ED presentation were evaluated by a deep learning artificial intelligence (AI) system and compared with the Radiographic Assessment of Lung Edema (RALE) score, calculated by two experienced radiologists. Death and critical COVID-19 (admission to intensive care unit (ICU) or deaths occurring before ICU admission) were identified as clinical outcomes. Independent predictors of adverse outcomes were evaluated by multivariate analyses. RESULTS: Six hundred ninety-seven 697 patients were included in the study: 465 males (66.7%), median age of 62 years (IQR 52-75). Multivariate analyses adjusting for demographics and comorbidities showed that an AI system-based score >/= 30 on the initial CXR was an independent predictor both for mortality (HR 2.60 (95% CI 1.69 - 3.99; p < 0.001)) and critical COVID-19 (HR 3.40 (95% CI 2.35-4.94; p < 0.001)). Other independent predictors were RALE score, older age, male sex, coronary artery disease, COPD, and neurodegenerative disease. CONCLUSION: AI- and radiologist-assessed disease severity scores on CXRs obtained on ED presentation were independent and comparable predictors of adverse outcomes in patients with COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov NCT04318366 ( https://clinicaltrials.gov/ct2/show/NCT04318366 ). KEY POINTS: * AI system-based score >/= 30 and a RALE score >/= 12 at CXRs performed at ED presentation are independent and comparable predictors of death and/or ICU admission in COVID-19 patients. * Other independent predictors are older age, male sex, coronary artery disease, COPD, and neurodegenerative disease. * The comparable performance of the AI system in relation to a radiologist-assessed score in predicting adverse outcomes may represent a game-changer in resource-constrained settings.