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Rapid multiplex polymerase chain reaction (PCR) assays simultaneously detect several respiratory viral pathogens with high sensitivity. Maximizing detection of influenza at the point of care has the potential to reduce unnecessary antibiotic use, laboratory tests and hospitalizations. However, the cost-effectiveness of rapid multiplex PCR assays for influenza has not been compared with other diagnostic methods in children.For children presenting to the emergency department with influenza-like illness, we compared costs and outcomes using 4 different testing strategies for detection of influenza: (1) a rapid multiplex PCR platform (FilmArray); (2) traditional PCR; (3) direct-fluorescent antibody and (4) rapid antigen tests. Costs were assessed from the hospital perspective, and effectiveness was defined as quality-adjusted life years (QALYs). Input parameters were obtained from previous studies, and the model was run separately for children aged 3–36 months and 3–18 years.Rapid multiplex PCR testing was the most effective testing strategy for children in both age groups. The incremental cost-effectiveness when compared with rapid antigen tests was $115,556 per QALY for children aged 3–36 months and from $228,000 per QALY for children aged 3–18 years. The cost-effectiveness of rapid multiplex PCR was sensitive to estimates for influenza prevalence, the proportion of patients treated with antivirals and the cost per test.Our model identifies scenarios in which identification of influenza in the emergency department using rapid multiplex PCR testing is a cost-effective strategy for infants and children 3 months through 18 years. Including detection of other respiratory viruses in the analysis would further improve cost-effectiveness.