Objectives: To assess gender-specific impact of genital warts on health-related quality of life (HRQoL), and to explore to what extent sexual characteristics and clinical symptoms influenced the impact on emotional and sexual well-being of both sexes. Methods: Sexual and clinical characteristics were collected of persons diagnosed with genital warts at STI clinics. HRQoL was measured using two measurement tools: 1) the generic EQ-5D; and 2) the genital warts-specific CECA-10 existing of an emotional well-being and a sexual activity dimension. The EQ-5D scores were compared with scores of the general population. Descriptive analyses were used to explore characteristics associated with HRQoL scores stratified for gender. Results: The HRQoL-measurement tools showed that genital warts have especially an emotional impact. The impact of genital warts on HRQoL was larger in women than in men. In addition, the CECA-10 showed that in women the impact of genital warts on sexual activity was influenced by age, relationship status and number of warts. No related factors were seen in men. Conclusions: Genital warts have a larger impact on women than on men. In women, sexual and clinical factors influenced the impact of genital warts on well-being, whereas in men no such factors were found.