Purpose Clinical case series suggest that the impact of interstitial cystitis on quality of life is severe and debilitating, however, little epidemiologic information is available. We examined the impact of interstitial cystitis on quality of life in a population based cohort of United States women. Materials and Methods We collected multidimensional measures of quality of life from 159,419 participants in the Nurses’ Health Study I and II using a validated instrument, the Medical Outcome Study Short-Form 36 Health Survey Instrument. This instrument measures physical function, role limitations due to physical and emotional problems, bodily pain, vitality, social function and mental health. Quality of life measures were collected on 99 women with prevalent self reported interstitial cystitis confirmed by medical record review. Results After adjusting for age and co-morbid conditions, women with interstitial cystitis had significantly lower quality of life scores in 4 of the 7 quality of life dimensions, including role/physical (β −13.1, p <0.001), bodily pain (β −9.8, p <0.001), vitality (β −7.7, p <0.001) and social function (β −7.2, p <0.001) compared to women without interstitial cystitis. Women with interstitial cystitis experienced less decrement in physical function compared to women with rheumatoid arthritis but more compared to women with hypertension. In addition, they experienced greater differences in vitality and mental health than women with rheumatoid arthritis or hypertension. Conclusions The quality of life among women with interstitial cystitis was especially limited in the psychosocial dimensions, such as vitality and mental health. Future research on interstitial cystitis should incorporate multidimensional measures of quality of life, especially with respect to response to the various treatments.