Interdigital tinea pedis is the most frequent presentation, as well as the most severe clinical form of tinea pedis, constituting a therapeutic challenge. The aim of the study was to evaluate the effectiveness and tolerability of two concentrations of Ageratina pichinchensis extract (encecalin content, 0.76 and 1.52%, respectively) on patients with clinical and mycological diagnosis of chronic interdigital tinea pedis. By means of a randomized, double-blind clinical trial, three groups of patients were treated topically for 4 weeks with a cream containing the following: Group I-the lower concentration of A. pichinchensis extract, group II-the higher concentration, group III-2% ketoconazole. One hundred and sixty (160) ambulatory patients of either sex between the ages of 18 and 65 years were enrolled. The primary outcome variables were: clinical effectiveness, mycological effectiveness, therapeutic cure, tolerability, and treatment compliance. The secondary outcome variable was therapeutic success. At the end of treatment, therapeutic cure was achieved by 34.1, 41.8, and 39.53% of Groups I, II, and III, respectively. No statistical difference between the groups was observed. Both treatments were effective for the treatment of interdigital-type tinea pedis, while better results were observed on patients that received the higher concentration of the extract.