OBJECTIVES: Although several studies have described the burden of Premenstrual Dysphoric Disorder (PMDD) impacts women's lives, few undertook a quantitative approach. This study is an attempt to quantify the burden of PMDD on health-related quality of life (HRQoL) in comparison to specific chronic conditions in the US general population. METHODS: The burden of PMDD on HRQoL was estimated by comparing SF-12 scores between women identified as being “at risk for PMDD” with SF-12 scores observed in the general US population. Additional comparisons were made to several chronic health conditions. SF-12 normative values of the general population were estimated through regression adjusted to match the age and disease comorbidity of the PMDD patient group. Significance tests between the means across samples were compared. Medical expenditures were estimated and compared for women who were “at risk for PMDD” and women with no reported chronic conditions. RESULTS: All SF-12 measures of PMDD were significantly below the adjusted US general population norms. The burden of PMDD was greater on mental/emotional than on physical HRQoL. The burden of PMDD on HRQoL was greater than that of chronic back pain; similar to type 2 diabetes, hypertension, osteoarthritis and rheumatoid arthritis; and largely comparable to depression. Age, PCS, and MCS scores were used to predict monthly medical expenditures using data from the annual Medical Expenditures Panel Survey (2001). The mean predicted monthly medical expenditure for women “at risk for PMDD” was $222.3 (SD=$107.3) and $134.0 (SD=$43.4) for women with no reported chronic conditions (p < .0001). CONCLUSION: PMDD is associated with substantial burden on physical and mental aspects of HRQoL, and may be related to increased medical expenditures.