Background  A new 8% ciclopirox‐medicated nail lacquer (P‐3051), based on a new technology, revealed superior properties in terms of affinity to keratin, nail permeation, and ease of use. Objective  This study aims to assess the efficacy and safety of P‐3051 vs. the market 8% ciclopirox nail lacquer. Methods  This is a multicentre, randomized, three‐arm, placebo‐controlled, parallel groups, evaluator‐blinded study. Overall, 467 patients with onychomycosis of at least one big toenail were randomized to receive P‐3051, the reference drug or placebo in a 2 : 2 : 1 ratio for a 48‐week treatment by daily application, followed by a 12‐week follow‐up. Results  The study satisfied its objective by demonstrating that P‐3051 was both superior to placebo and non‐inferior to reference in the complete cure rate after a 48‐week active treatment period. Switching the non‐inferiority to superiority hypothesis, the superiority of P‐3051 vs. reference was nearly significant at week 48 (confirmed at week 52), and it was significant at week 60 (cure rate for P‐3051 is 119% higher than reference; P < 0.05). Altogether, the results on primary endpoint exceed expectations; superiority test was performed also on secondary endpoints to confirm the superiority trend of the study. At the end of follow‐up, percentages of patients who achieved the endpoint ‘responder’ in the P‐3051 group were 66% higher than reference (P < 0.05), and those who achieved the endpoint ‘decrease of diseased nail’ were 40% higher (P < 0.05). Conclusion  Ciclopirox 8% hydrolacquer is more active than reference ciclopirox nail lacquer in the treatment of onychomycosis. Conflicts of interest None declared.