BACKGROUND The burden of anogenital warts will be a determining factor when making decisions about the type of human papillomavirus (HPV) vaccine to be used (bivalent or quadrivalent) and whether to vaccinate males. We conducted a multicenter prospective study to (1) describe the impact of anogenital warts on quality of life and (2) estimate the quality-adjusted life-years (QALYs) lost due to anogenital warts. METHODS Between September 2006 and February 2008, 272 patients with a first or recurrent episode of anogenital warts were recruited from the clinical practices of 42 physicians across Canada. Quality of life was measured at recruitment, and 2 and 6 months later with the EuroQol, Short Form-12, short Spielberg State-Trait Anxiety Inventory, and HPV impact profile. The duration of an episode and QALYs lost due to anogenital warts were estimated among 51 incident cases recruited within 90 days of disease onset. RESULTS Anogenital warts had a significant impact on the quality of life. This negative impact was similar for first and recurrent episodes, and lasted as long as lesions persisted. Anogenital warts had the greatest negative impact on usual activities, pain/discomfort, and anxiety/depression, and on self-image, sexual activity, and partner issues and possible transmission. The median duration of a first anogenital wart episode amongst incident cases was 125 days and resulted in QALYs lost of 0.017 to 0.041, which is equivalent to 6 to 15 days of healthy life lost. CONCLUSIONS The burden of anogenital warts is substantial and should be considered by physicians and public health officials when making recommendations about HPV vaccination..