en Pediatric Infectious Diseases Original Article Original Article <strong>Background</strong>: The global search for effective COVID-19 treatments extended to the use of ivermectin, a drug with potential antiviral properties. However, evidence remains conflicting, especially for children.&nbsp;<br> <strong>Objectives</strong>: This study aimed to investigate the efficacy and safety of ivermectin for treating COVID-19 in Iranian children through two independent randomized, placebo-controlled trials.&nbsp;<br> <strong>Methods</strong>: Two multicenter, randomized, double-blind, placebo-controlled clinical trials were conducted to evaluate the efficacy of ivermectin in 195 children with COVID-19, including 66 inpatients (35 in the ivermectin group and 31 in the placebo group) and 129 outpatients (70 in the ivermectin group and 59 in the placebo group). The treatment group received a daily oral dose of ivermectin (400 &mu;g/kg/day, 6 mg tablet) for three consecutive days, while the control group received an identical placebo. The primary outcome was disease prognosis. The secondary outcomes for inpatients included duration of hospitalization, need for pediatric intensive care unit (PICU) admission, need for oxygen, adverse events, and mortality. For outpatients, secondary outcomes were need for hospitalization, need for PICU admission, viral clearance, adverse events, and mortality.<br> <strong>Results</strong>: All inpatients in both ivermectin and placebo groups fully recovered from COVID-19. Among outpatients, 98.6% recovered after ivermectin use, and 100% recovered with placebo. A significant difference was found in the need for PICU admission among inpatients (2.8% in the ivermectin group and 25.8% in the placebo group; P=0.010). Additionally, viral clearance differed significantly, with more patients in the ivermectin group testing negative for COVID-19 on day six than in the placebo group (P=0.042). The length of hospital stay was similar for both groups.&nbsp;<br> <strong>Conclusions</strong>: Although ivermectin can reduce the need for PICU admission among inpatient children with COVID-19, it did not improve overall clinical recovery or length of hospital stay. For outpatients, ivermectin does not enhance recovery or reduce the need for hospitalization but showed promising viral clearance effects. Considering all aspects, the use of ivermectin in the treatment of children with COVID-19 cannot be recommended.&nbsp; Ivermectin, COVID-19, Children, Clinical trial 287 300 http://jpr.mazums.ac.ir/browse.php?a_code=A-10-369-8&slc_lang=en&sid=1 Azin Hajialibeig azin.hajialibeyg@gmail.com 100319475328460014017 100319475328460014017 No Pediatric Infectious Diseases Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran. Fatemeh Hosseinzadeh fatima.hzade@gmail.com 100319475328460014018 100319475328460014018 No Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran. Mahsa Kamali kamali2n@gmail.com 100319475328460014019 100319475328460014019 No Pediatric Infectious Diseases Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran. Mohammad Reza Navaeifar dr.navaifar@gmail.com 100319475328460014020 100319475328460014020 No Pediatric Infectious Diseases Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran. Leila Shahbaznejad leilashahbaznezhad@gmail.com 100319475328460014021 100319475328460014021 No Pediatric Infectious Diseases Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran. Faezeh Sadat Movahedi f.movahedi69@gmail.com 100319475328460014022 100319475328460014022 No Pediatric Infectious Diseases Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran. Fereshteh Rostami-Maskopaee rostamiraha5@gmail.com 100319475328460014023 100319475328460014023 No Pediatric Infectious Diseases Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran. Mohammad Sadegh Rezai drmsrezaii@yahoo.com 100319475328460014024 100319475328460014024 Yes Pediatric Infectious Diseases Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran.