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A valid and reliable measure that captures onychodystrophy disease severity is important for both clinical and research applications. Three hundred and twenty-two patients at two Veterans Affairs Medical Centers with clinical evidence of onychodystrophy suggesting onychomycosis (at least 25% in a distal subungual pattern) were examined using Naildex parameters. Naildex scores were calculated by a combination of: per cent of each nail infected, area of each nail and number of infected nails. Patients also completed a nail-specific quality of life questionnaire (NailQoL) and nail samples were collected and examined mycologically. Data was analysed for all enrolled patients (n = 322) and patients with mycologically-confirmed onychomycosis (n = 243). Inter-rater reliability was calculated from two examiners who each evaluated 17 patients with mycologically-confirmed onychomycosis. Significant correlations (P < 0.01) between Naildex and NailQoL as well as proxy measures (duration of infection) indicated construct validity of the instrument for all patients as well as mycologically-confirmed cases. Strong correlation (r = 0.754, P < 0.01, n = 17) indicated high inter-rate reliability. This pilot evaluation suggests that Naildex is a valid and reliable measure of onychomycosis severity.