Patients with toenail onychomycosis remain a therapeutic challenge despite the introduction of new systemic therapies. Around 20% of patients remain uncured even with optimal oral therapy, but the reasons for treatment failure are unclear. Thus far there are no data to suggest that treatment failures can be identified on the basis of their presenting features or progress during treatment. In a series of patients, we have attempted to identify clinical parameters that determine the patient response to 12 weeks of oral terbinafine for confirmed dermatophyte onychomycosis. As part of a dose-defining randomized multicentre study, 35 patients were followed for 48 weeks. The unaffected nail length, growth rate, hyperkeratosis, onycholysis and presence of a dermatophytoma were assessed prospectively. To confirm our findings, at the end of the study period we analysed retrospectively photographs that had been taken regularly throughout the trial. The average degree of hyperkeratosis was less severe in the group achieving a disease-free nail, meaning clinical and mycological cure. For mycological cure alone, no predictive factors could be identified.