Background: Onychomycosis is a widespread refractory disease deleteriously affecting quality of life via social stigma and disrupting daily activities. Many physicians perceive onychomycosis as a cosmetic rather than a medical problem. Objective: Our purpose was to develop a questionnaire-based instrument to quantify the impact of onychomycosis on patients’ quality of life. Methods: The questionnaire was developed and validated in a multinational cross-sectional study. Completed questionnaires from 532 patients were analyzed: 284 toenail, 248 fingernail (onychomycosis or paronychia). Results: The degree of quality of life impairment from onychomycosis varied by country studied, possibly reflecting cross-national health perception differences. Longer duration of disease, greater involvement of individual nails, and greater number of nails involved were associated with more serious adverse effects. Many physicians underestimated the associated degree of pain. Conclusion: The study confirms that onychomycosis physically and psychologically affects patients’ lives. The questionnaire may be a valuable tool in evaluating the effect of therapeutic agents on quality of life of patients with onychomycosis. (J Am Acad Dermatol 1999;41:189-96.)