Background: Patients with onychomycosis may experience physical impairment and psychological and social limitations related to their infection. Objective: The object of this study was to compare health-related quality-of-life scores of patients with onychomycosis with those of a control group. Methods: The interview instrument included scales of general measures, disease-specific factors, and issues specifically related to onychomycosis symptoms; the onychomycosis group also was questioned about past treatment and attitude towards treatment. Results: A total of 299 persons with onychomycosis and 381 controls were interviewed. Demographic factors were similar except for gender and age. Analyses adjusted for these differences. All general quality-of-life scores but one were significantly lower in the onychomycosis group. For responses to questions related specifically to nails, the onychomycosis group reported significantly more problems with physical appearance than did controls (p < 0.001); the greatest absolute differences were for physical activities involving the feet. The majority (88%) of the onychomycosis group indicated they would take oral medication even if it had short-term side effects. Conclusion: Onychomycosis affects generic health-related quality-of-life measures less than other variables. The greatest impact is on onychomycosis-specific measures. Because patients are willing to try treatment, many of these quality-of-life concerns can be addressed by newer oral treatments. (J Am Acad Dermatol 1998;38:S64-8.)