Background Despite the development and application of vaccines against SARS-CoV-2 around the world, the scientific community still tried to find some therapies to avoid or ameliorate the fatal evolution of the COVID-19. Since the publication of the potential use of Ivermectin as a treatment against the disease, a pleiad of information about it has been published. However, the evidence is not strong or weak enough to conclude its usefulness in the clinical evolution of patients infected with SARS-CoV-2. We evaluate the efficacy and safety of ivermectin in the treatment of Mexican patients with asymptomatic and mild COVID-19 in a three-day administration in comparison to placebo. Methods A randomized, double-blind, placebo-controlled trial was carried out in 66 adults with asymptomatic and mild COVID-19. Patients were randomly assigned 1:1 ratio to Ivermectin plus acetaminophen or placebo plus acetaminophen. The primary endpoint was the proportion of subjects without a disease progression to severity according to COVID-19 guidelines by the National Institutes of Health (NIH) since randomization to 14 days. Results None of the participants presented progression to a severe state in either group. Viral load was measured on Days 1, 5 and 14. No significant differences were observed in baseline or 14-day between groups (p = 0.720 and 0.362, respectively). However, on Day 5, a significant difference in viral load was observed between groups (p = 0.039). The frequency of symptoms was similar between groups, and no significant differences were observed. The most frequent symptom was cough. One severe adverse event associated with SARS-CoV-2 infection was observed in the ivermectin group. Conclusions At standard doses, ivermectin is not effective in the progression to severe state and reducing symptoms in adults with asymptomatic and mild COVID-19. Trial registration The study was registered with ClinicalTrial.gov (NCT04407507)