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. We conducted a survey of sexual and clinical characteristics from 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 including 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. The HRQoL-measurement tools showed that genital warts have especially an emotional impact. The impact of genital warts on HRQoL was greater for women than for 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. Genital warts have a greater 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.