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Background Influenza-like illness (ILI) definitions have been infrequently studied in young children. Despite this, clinical definitions of ILI play an important role in influenza surveillance. This study aims to identify clinical predictors of influenza infection in children ≤5 years old from which age-specific ILI definitions are then constructed. Methods Children aged 6–59 months with a history of fever and acute respiratory symptoms were recruited in the Western Australia Influenza Vaccine Effectiveness (WAIVE) Study. Clinical data and per-nasal specimens were obtained from all children. Logistic regression identified significant predictors of influenza infection. Different ILI definitions were compared for diagnostic accuracy. Results Children were recruited from 2 winter influenza seasons (2008–2009; n = 944). Of 919 eligible children, 179 (19.5%) had laboratory-confirmed influenza infection. Predictors of infection included increasing age, lack of influenza vaccination, lower birth weight, fever, cough, and absence of wheeze. An ILI definition comprising fever ≥38°C, cough, and no wheeze had 58% sensitivity (95% confidence interval [CI], 50–66), 60% specificity (95% CI, 56–64), 26% positive predictive value (95% CI, 21–31), and 86% negative predictive value (95% CI, 82–89). The addition of other symptoms or higher fever thresholds to ILI definition had little impact. The Centers for Disease Control and Prevention definition of ILI (presence of fever [≥37.8°C] and cough and/or sore throat) was sensitive (92%; 95% CI, 86–95), yet lacked specificity (10%; 95% CI, 8–13) in this population. Conclusions Influenza-like illness is a poor predictor of laboratory-confirmed influenza infection in young children but can be improved using age-specific data. Incorporating age-specific ILI definitions and/or diagnostic testing into influenza surveillance systems will improve the accuracy of epidemiological data. [ABSTRACT FROM AUTHOR]