Abstract Objectives We perform a cost-effectiveness analysis (CEA) and budget impact analysis (BIA) of baloxavir marboxil compared to current care in the Netherlands for patients at risk of influenza-related complications, including patients with comorbidities and the elderly. Methods In the CEA, a decision tree model was developed to assess the cost-effectiveness of baloxavir marboxil for a cohort of 52-year-olds from a societal perspective. A lifetime horizon was taken by incorporating the quality-adjusted life expectancy. The BIA included different epidemiological scenarios, estimating different plausible epidemiological scenarios for seasonal influenza considering the whole Dutch population with an increased risk of influenza complications. Results The base-case ICER was estimated to be €8,300 per QALY. At the willingness-to-pay threshold of €20,000 per QALY, the probability of being cost effective was 58%. The base-case expected budget impact was €5.7 million on average per year, ranging from €1.5 million to €10.5 million based on the severity of the influenza epidemic and vaccine effectiveness. Conclusion In the Netherlands, baloxavir is a cost-effective treatment option for seasonal influenza, with a base-case ICER of €8,300 per QALY for the population aged 60 years and over and patients at high risk of influenza-related complications. For a large part, this ICER is driven by the reduction of the illness duration of influenza and productivity gains in the working population.