Background: Poisoning comprises about 7% of accidents in children under 5-year-old and 2% of all pediatric deaths in developing countries. To warn against and prevent future potential poisoning with opioid substances, this comparative study was conducted on pediatric cases referred to the 17th Shahrivar Hospital in Rasht, Iran, in 2006 and 2018. Methods: In this retrospective, cross-sectional study, all hospitalized pediatric cases diagnosed with opioid poisoning in 2006 and 2018 were investigated systematically. The demographic data, such as age, gender, city or village of residence, the poisoning substances involved, and the clinical outcomes were extracted from the medical records and entered on an appropriately-designed form. The data analysis was performed, using SPSS software, version 21. Results: Fifty pediatric cases were examined with a mean age of 44.38±3.8 months old. Among these cases, 14 children had been poisoned, 13 of whom with opium and one with morphine in 2006; while in 2018, 36 children had been poisoned with methadone and only one with opium. Conclusion: Comparing years 2006 with 2018, a considerable increase in pediatric opioid poisoning cases was observed with a tendency toward methadone being the substance involved. The occurrences might be due to unsafe access of unaware children to this drug, especially after the initiation of methadone maintenance treatment for opiate addicts, who were mainly the parents or relatives living in the same household.