We aimed to determine whether there are signs or symptoms that could help clinicians to distinguish between influenza and other respiratory infections. The clinical data for this matched case-control analysis were derived from a 2-year prospective cohort study of respiratory infections among children aged≤13 years. At any signs of respiratory infection, the children were examined and nasal swabs were obtained for virologic analyses. Cases were 353 children with laboratory-confirmed influenza and controls were 353 children with respiratory symptoms who tested negative for influenza. Cases and controls were matched for gender, age, and timing of the visit. In the multivariate conditional logistic regression analyses, fever was the only sign that independently predicted influenza virus infection, with odds ratios ranging from 13.55 (95% confidence interval [CI], 6.90-26.63) to 50.10 (95% CI, 16.25-154.45), depending on the degree of fever. In all analyses, the predictive capability of fever increased with incremental elevations in the child's temperature. The likelihood ratio of fever≥40.0°C in predicting influenza was 6.00 (95% CI, 2.80-12.96). Among unselected children seen as outpatients during influenza outbreaks, fever is the only reliable predictor of influenza virus infection. The optimal use of influenza-specific antiviral drugs in children may require virologic confirmation.