OBJECTIVE: This study evaluates the projected cost-effectiveness of antiviral treatments (amantadine or oseltamivir) with and without the use of influenza rapid tests in children. METHODS: A decision tree was developed to predict costs and health effects of 5 strategies: no antiviral treatment, empirical treatment with amantadine, empirical treatment with oseltamivir, testing then treatment with amantadine, and testing then treatment with oseltamivir. The target population was stratified by age (6-23 mos, 2 yrs, 3-4 yrs, 5-11 yrs, and 12-17 yrs) and risk status (high or low risk for influenza-related complications). Probabilities and costs (direct and opportunity) for uncomplicated influenza, influenza-like illness, outpatient visits, hospitalizations, deaths, effectiveness of antiviral treatments, treatment adverse events, and characteristics of influenza rapid tests were based on primary and secondary data. Quality adjustments (time-tradeoff amounts) for influenza-related events were based on primary data from a telephone survey (n = 112). Incremental cost-effectiveness ratios in dollars per quality-adjusted life year (QALY) were calculated. RESULTS: For an unvaccinated population, the base case cost per QALY for empirical treatment with amantadine was less than $1000 for all subgroups and for empirical treatment with oseltamivir ranged from less than $1000 to $8000 depending on age and risk status. Results were sensitive to influenza illness rate, proportion of influenza-like illness that is confirmed influenza, and influenza vaccination status. Testing and treatment options were more costly and less effective than empirical treatment options. Probabilistic sensitivity analysis suggests that empirical treatment with amantadine has similar cost-effectiveness ratios under many scenarios while the cost-effectiveness ratios of empirical treatment with oseltamivir show wider variability. CONCLUSIONS: Empirical treatment with amantadine during peak influenza season is notably more cost-effective than empirical treatment with oseltamivir. Both reductions in test prices and improvement in accuracy of rapid influenza tests will be needed to make testing and treatment strategies attractive alternatives.