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Introduction: Trivalent, intranasal, live attenuated influenza virus vaccine (LAIV) is safe and clinically effective in healthy, working adults. However, the potential economic benefits of vaccinating this population are still uncertain. We therefore conducted a cost benefit analysis of influenza vaccination of healthy working adults utilizing clinical outcome data from a trial of LAIV in healthy working adults.Methods: This cost benefit analysis was based on the results of a multi-center, randomized, double blind placebo controlled trial that assessed the clinical effectiveness of LAIV in healthy working adults. Outcomes from the trial that were included in the cost benefit analysis were days of work missed, days working but at reduced effectiveness, and days with a health care provider visit due to at least one of the following symptoms: fever, runny nose, sore throat, cough, headache, muscle aches, chills, or tiredness/weakness. Cost data were obtained from nationally representative databases. Probability distributions for the key model variables were defined, and Monte Carlo simulation was used to estimate the mean break even costs for vaccine and its administration. Sensitivity analyses explored how changes in the variables affected these estimates.Results: There were 4561 participants in the clinical trial. LAIV lowered work loss due to illness symptoms by 18% (relative rate [RR] 0.82, 95% confidence interval [CI] 0.74–0.91), days of working at reduced effectiveness by 18% (RR 0.82, 95% CI 0.74–0.91), and days with a health care provider visit by 13% (RR 0.87, 95% CI 0.77–0.98). The mean break even cost for vaccine and its administration was US$ 43.07 per person vaccinated (5–95% percentiles, US$ 25.72–58.92). Major cost drivers were hourly wage and vaccine effectiveness in reducing productivity losses and health care use.Conclusion: This cost benefit analysis based on the results of the LAIV trial provides additional evidence that influenza vaccination may provide both health and economic benefits for healthy, working adults. [Copyright &y& Elsevier]