Background: Onychomycosis, or fungal nail infection, is the cause of 50% of onychopathies seen by podiatric physicians. This pathology is accompanied by a negative psychosocial component because of its effect on self-image, which is an essential part of social relations. Conventional pharmacologic treatment based on antifungal agents is lengthy and expensive and has a high abandonment rate and a low cure rate. Therefore, a faster and more efficient solution has been sought using laser treatment. However, studies on the efficacy of this physical method are not conclusive due to the lack of uniformity in the method used to apply the laser and an objective method to measure the results. The aim of this study was to measure the efficacy of laser treatment of onychomycosis by microbiological cure and clinical evolution using the Onychomycosis Severity Index. Methods: A prospective study with a strictly repetitive protocol of Nd:YAG 1,064-nm laser was applied to 50 participants with onychomycosis in the first toe, following the manufacturer's instructions. The efficacy of the treatment on fungal infection was measured by microbiological culture before and after treatment. The clinical evolution of the nail dystrophy was quantitatively evaluated using the Onychomycosis Severity Index. Results: The efficacy of Nd:YAG 1,064-nm laser in eliminating fungal infection was 30% (15 participants). However, significant improvement in nail appearance (dystrophy) was observed in 100% of patients (P < .001). Conclusions: Laser treatment has relatively low efficacy in treating fungal infection but results in an objective improvement in the clinical appearance of the nail in 100% of patients.