OBJECTIVES: Estimate annual direct (medical expenditure) and indirect (absenteeism and short-term disability) costs for women with uterine fibroids (UF). METHODS: We compared 12-month direct costs among women aged 18-54 with clinically-significant, symptomatic UF (admission, emergency visit, or >2 office visits >30 days apart with a UF diagnosis) to a 1:1 propensity score matched cohort of women without UF, using the MarketScan Commercial Claims and Encounters insurance database data from for 2000 – 2004. We also compared indirect costs for the sub-sample of women with available data. Exponential conditional regression analysis controlled for confounding factors, and costs were adjusted to 2004 levels. RESULTS: Sample sizes for the direct and indirect costs analyses were 38,020 and 1,820, respectively. Mean 12-month direct costs for women in the UF group were $11,720 vs. $3,257 for controls (women without diagnosed or treated fibroids). Mean 12-month indirect costs were $11,752 and $8,083 for women in the UF group and controls, respectively. Estimated direct costs attributable to UF were therefore $8,463 (p<0.001) and indirect costs were $3,669 (p<0.001). Employers' share of direct costs ranged from 84.1% to 87.5%. CONCLUSION: Direct and indirect costs of uterine fibroids represent a substantial burden to employers. Treatment options aimed at reducing symptoms and resultant absenteeism are needed to improve women's health and productivity.