To investigate the efficacy and safety of carbon dioxide (CO2) laser cauterization in the treatment of pediatric congenital pyriform sinus fistula (CPSF), and to track and follow up the long-term outcome of the postoperative patients. This retrospective study was conducted at a single center, where clinical data and follow-up information of children with CPSF who underwent CO2 laser cauterization with the assistance of a suspension laryngoscope and microscope were collected and analyzed their clinical characteristics and prognosis. Subsequently, multiple logistic regression analysis was performed to identify potential predictors of the number of laser cauterization procedures. A total of 238 children diagnosed with CPSF were recruited for this study, with 235 patients successfully achieving closure of the internal fistula through one or more CO2 laser cauterization procedures without recurrence. The median duration of follow-up was 6.46 (5.20, 7.64) years. Merely three patients (1.3%) developed recurrent cervical infection and eventually underwent open neck surgery. There were no instances of permanent perioperative complications throughout the follow-up. Additionally, our analysis revealed that the age at the first operation of CO2 laser cauterization was an independent risk factor associated with the number of operations. The CO2 laser cauterization for children with CPSF is an effective and safe treatment with a low recurrence rate and minimal complications during the follow-up period. Consequently, it is advisable to consider CO2 laser cauterization as a viable therapeutic option for managing pediatric CPSF. 4 Laryngoscope, 2024.