OBJECTIVES: The objective of the study was to examine changes in health-related quality of life (HRQOL) in an observational database of patients with onychomycosis receiving various treatments by either dermatologists or podiatrists. METHODS: Dermatologists or podiatrists at 8 US sites reported on clinical outcomes at baseline and follow-up (4 and 9 months). Patients completed a validated HRQOL questionnaire at the same time points that measured the impact of onychomycosis on generic (general health perception, pain, mental health, social functioning, health distress, physical functioning, and health transition) and disease-specific items (toe symptom frequency, toe symptom bother, problems with appearance, problems with activities, stigma and satisfaction with treatment). RESULTS: One hundred and thirteen patients completed the questionnaire at baseline and follow-up. Forty eight percent of patients were treated by dermatologist, 52% by podiatrist. Patients were predominately male (58%). At month 9, patients treated with oral anti-fungal therapy had significant improvements in physical functioning, toenail symptoms, toenail bother, problems with appearance and activities, stigma, pain and satisfaction with treatment (p<0.01) when compared with patients treated with non-oral therapy. CONCLUSION: The data indicates that patients with onychomycosis who seek treatment with oral therapy report significant improvement in HRQOL and satisfaction compared with patients treated with non-oral therapy.