RationaleEpilepsy is a frequent neurologic condition with important financial strains on the US healthcare system. The co-occurrence of multiple chronic conditions (MCC) may have additional financial repercussions on this patient population. We aimed to assess the association of coexisting chronic conditions on healthcare expenditures among adult patients with epilepsy. MethodsWe identified a total of 1,942,413 adults (≥18 years) with epilepsy using the clinical classification code 83 from the MEPS-HC (Medical Expenditure Panel Survey Household Component) database between 2003 and 2014. Chronic conditions were selected using the clinical classification system (ccs), and categorized into 0, 1, or 2 chronic conditions in addition to epilepsy. We computed unadjusted healthcare expenditures per year and per individual (total direct healthcare expenditure, inpatient expenditure, outpatient expenditure, prescription medication expenditure, emergency room visit expenditure, home healthcare expenditure and other) by number of chronic conditions. We applied a two-part model with probit (probability of zero vs non-zero cost) and generalized linear model (GLM) gamma family and log link (for cost greater than zero) to examine the independent association between chronic conditions, and annual expenditures per individual, generating incremental costs with 0 chronic condition as reference. ResultsOver half of the patients with epilepsy had at least two chronic conditions (CC). Yearly, for each patient with one and two chronic conditions, unadjusted total healthcare expenditures were two times ($10,202; 95 %CI $6,551–13,853) to nearly three times ($21,277; 95 %CI $12,971–25,583) higher than those with no chronic conditions ($6,177; 95 %CI $4,895–7,459), respectively. In general healthcare expenditures increased with the number of chronic conditions for pre-specified cost categories. The incremental (adjusted) total healthcare expenditure increased with the number of chronic conditions (1CC vs 0 CC: $3,238; 95 %CI $524–5,851 p-value = 0.015 and ≥2 CC vs 0 CC: $8,145; 95 %CI $5,935–10,895 p-value < 0.001). In general, for all cost categories, incremental healthcare expenditures increased with the number of chronic conditions with the largest increment noted between those with 2 CC and those with 0 CC for inpatient ($2,025: 95 %CI $867–3,1830), outpatient ($2,141; 95 %CI $1,321–2,962), and medication ($1,852; 95 %CI $1,393–2,310). ConclusionChronic conditions are frequent among adult patients with epilepsy and are associated with a dose–response increase in healthcare expenditure, a difference driven by inpatient, outpatient, and medication prescription expenditures. Greater coordination of epilepsy care accounting for the presence of multiple chronic conditions may help lower the cost of epilepsy.