OBJECTIVES: Economic models assessing vaccinations commonly assume that inflation-adjusted vaccine costs are constant over time. This study assessed this assumption using historical vaccine cost data. METHODS: Private sector and CDC contracted vaccine cost data (2001-2023) were collected from the CDC Vaccine Price List and converted to US023 to adjust for inflation. Trends in inflation-adjusted costs were described, and the annual percent changes in costs were calculated for each vaccine. RESULTS: Changes in cost varied by vaccine. The average inflation-adjusted private sector costs increased by 0.9 % (IQR: -0.4 %-2.6 %) and 1.4 % (IQR: -0.4 %-3.2 %) annually among pediatric and adult vaccines, respectively, while CDC contracted costs increased by 0.9 % (IQR: 0.2 %-1.2 %) and 1.0 % (IQR: -0.8 %-2.1 %) annually among pediatric and adult vaccines, respectively. CONCLUSIONS: Inflation-adjusted vaccine costs increased on average since 2001, highlighting limitations of constant cost assumptions. These findings can inform cost-effectiveness analyses of multi-year vaccination programs and policies.