Real-time reverse-transcriptase polymerase chain reaction (RT-PCR) has been the gold standard for diagnosing coronavirus disease 2019 (COVID-19) but has a lag time for the results. An effective prediction algorithm for infectious COVID-19, utilized at the emergency department (ED), may reduce the risk of healthcare-associated COVID-19. To develop a prototypic prediction model for infectious COVID-19 at the time of presentation to the ED. Retrospective cohort study of all adult patients admitted to Singapore General Hospital (SGH) through ED between March 15, 2020, and December 31, 2022, with admission of COVID-19 RT-PCR results. Two prediction models were developed and evaluated using area under the curve (AUC) of receiver operating characteristics (ROC) to identify infectious COVID-19 patients (cycle threshold (Ct) of <25). Total of 78,687 patients were admitted to SGH through ED during study period. 6,132 of them tested severe acute respiratory coronavirus 2 positive on RT-PCR. Nearly 70% (4,226 of 6,132) of the patients had infectious COVID-19 (Ct<25). Model that included demographics, clinical history, symptom and laboratory variables had AUROC of 0.85 with sensitivity and specificity of 80.0% & 72.1% respectively. When antigen rapid test results at ED were available and added to the model for a subset of the study population, AUROC reached 0.97 with sensitivity and specificity of 95.0% and 92.8% respectively. Both models maintained respective sensitivity and specificity results when applied to validation data. Clinical predictive models based on available information at ED can be utilized for identification of infectious COVID-19 patients and may enhance infection prevention efforts.