Objective: To establish and validate a new system to define the severity of onychomycosis. The Onychomycosis Severity Index (OSI) score is obtained by multiplying the score for the area of involvement (range, 0-5) by the score for the proximity of disease to the matrix (range, 1-5). Ten points are added for the presence of a longitudinal streak or a patch (dermatophytoma) or for greater than 2 mm of subungual hyperkeratosis. Mild onychomycosis corresponds to a score of 1 through 5; moderate, 6 through 15; and severe, 16 through 35. Design: Consensus conference. Setting: Teleconference. Participants: The consensus group included 5 dermatologists, 1 dermatology resident with an interest in nail disorders, and a statistician. The meetings were held by closed teleconference. Main Outcome Measures: Index reliability. Results: The reliability of the OSI system was assessed in 2 steps. The first assessment included 37 dermatologists who scored 8 photographs of onychomycosis after being taught how to use the OSI. The scoring system showed very high reliability (Cronbach α = 0.99 and intraclass correlation coefficient [ICC] = 0.95). The second assessment entailed evaluation of 49 nails by 3 dermatologists, including an expert in the OSI. This assessment was conducted at the University of Alabama at Birmingham and at the Oregon Dermatology and Research Center, Portland. The scoring system showed very high reliabilities at both sites (Cronbach α = 0.99 and ICC = 0.96 at the University of Alabama at Birmingham, and Cronbach α = 0.98 and ICC = 0.93 at the Oregon Dermatology and Research Center). Conclusion: The OSI is a new, simple, objective, reproducible numeric system to grade the severity of onychomycosis. ©2011 American Medical Association. All rights reserved.