OBJECTIVES: Adults with migraine possess significant economic burden to the United States (US), however, it remains unknown whether there have been changes in the economic burden among adults with migraine in the past decade given therapeutic advances. Therefore, we aimed to estimate trends of incremental direct healthcare expenditures among adults with migraine as compare to adults without migraine between 2004 and 2013. METHODS: We analyzed trends of 10-years of data representing a weighted population of 228,000,000 US adults (≥ 18 years) from the Medical Expenditures Panel Survey (MEPS). We used two-part model to estimate the incremental total and types of annual healthcare expenditures among adults with migraine after adjusting for demographic, socioeconomic, health status, lifestyle risk factors and chronic conditions. All analyses accounted for complex survey design. Healthcare expenditures were inflated to 2013 constant US dollars. RESULTS: Adults with migraine had nearly 1.5 times greater unadjusted average annual total healthcare expenditures ($8,033, 95%CI: $7,458-$8,607) as compared to those without migraine ($5,118, 95%CI: $5,014-$5,222) over a period of 10-year.  As compared to those without migraine, adults with migraine have $1,393(95% CI: $759-$2,027) and $1,493 (95% CI: $665- $2,213) greater annual total healthcare expenditures in 2003/2004 and 2012/2013 in the adjusted model respectively. Adults with migraine did not have significant changes in the total healthcare expenditures in 2012/2013 as compared to 2004/2005 (changes: -$555, 95% CI: -$1,513- $403) in the adjusted model.  The estimated unadjusted total migraine healthcare expenditures in the US population were $56.3 billion/year and the adjusted total incremental expenditures were $11.6 billion/year. CONCLUSIONS: National Trends on incremental expenditures among adults with migraine suggest significant incremental burden as compared to those without migraine across the years. Therefore, the policy should be targeted to reduce the excess healthcare expenditures among individuals with migraine.