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Objectives: To determine the diagnostic yield of screening patients for SARS-CoV-2 who were admitted with a diagnosis unrelated to COVID-19 and to identify risk factors for positive tests., Design: Cohort from the Canadian COVID-19 Emergency Department Rapid Response Network registry., Setting: 30 acute care hospitals across Canada., Participants: Patients hospitalised for non-COVID-19-related diagnoses who were tested for SARS-CoV-2 between 1 March and 29 December 2020., Main Outcome: Positive nucleic acid amplification test for SARS-CoV-2., Outcome Measure: Diagnostic yield., Results: We enrolled 15 690 consecutive eligible adults who were admitted to hospital without clinically suspected COVID-19. Among these patients, 122 tested positive for COVID-19, resulting in a diagnostic yield of 0.8% (95% CI 0.64% to 0.92%). Factors associated with a positive test included presence of fever, being a healthcare worker, having a positive household contact or institutional exposure, and living in an area with higher 7-day average incident COVID-19 cases., Conclusions: Universal screening of hospitalised patients for COVID-19 across two pandemic waves had a low diagnostic yield and should be informed by individual-level risk assessment in addition to regional COVID-19 prevalence., Trial Registration Number: NCT04702945., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)