The goal of this study was to quantify the incremental direct medical and indirect work-loss costs associated with patients diagnosed with atopic dermatitis (AD). A de-identified administrative claims database was used comprising 5.1 million covered beneficiaries from 31 Fortune 500 self-insured employers between 1998 and 2005. Patients with at least two AD diagnosis claims (N = 13,749) were compared with three matched controls (based on yr of birth and gender) with no AD diagnosis (N = 41,247). In addition, a multivariate two-part regression analysis was used to isolate the cost increase attributable to AD by controlling for confounding factors such as age, gender, health plan type, comorbidities, organ transplantation, industry of employer, region, and year. Direct medical and indirect work-loss costs for the AD group were higher on average by $88 and $64 per patient per month, respectively (both P< .001). After multivariate adjustment, the total incremental cost per patient per month for the AD group was $83 (direct: $52, P< .001; indirect: $31, P< .001). Employer-payers experience a significant annual cost burden of $991 per patient attributable to AD. Employee disability and increased sick days account for 38% of the cost burden.