A multicenter retrospective analysis of 408 patients diagnosed with onychomycosis and attended at three tertiary care Spanish hospitals was conducted to assess the effectiveness and safety of a combined treatment with ciclopirox 8% hydroxypropyl chitosan (CPX 8% HPCH) nail lacquer and oral antifungal agents (terbinafine, itraconazole, and fluconazole). Data were extracted and analyzed using the EHRead® technology based on natural language processing and machine learning and using SNOMED CT terminology. The median age was 51 years with a ratio male: female close to 1. Repeated nail trauma was the most common risk factor (7.1%). More than half of patients (56.6%) underwent fungal culture. Terbinafine was used in 67.7% of patients, itraconazole in 20.8%, and fluconazole in 11.5%. Treatment synchronicity distribution revealed that 59.1% of patients started concomitant treatment with CPX 8% HPCH and oral antifungals, 27.9% had initial oral antifungals, and 13% had initial nail lacquer. The response to treatment (positive response 15.7%, presumed positive 59.8%) was unrelated to treatment synchronicity or type of antifungal agent. Erythema (5.6%), diarrhea (4.9%) and fever (4.2%) were the most frequently registered potential adverse events. The present findings provide valuable insights for physicians paving the way for better management of patients with onychomycosis.