Introduction: At the beginning of the COVID-19 epidemic, the French Addictovigilance Network alerted on the need to facilitate access to methadone, while maintaining the safety of its use, to avoid the occurrence of overdoses and deaths. The impact of the lockdown on methadone-use related hospitalizations (MUH) has not been analyzed at the national level. The objectives of the study were to assess the impact of the lockdowns on the incidence of the MUHs and describe the characteristics of patients and hospitalizations. Material and methods: This retrospective study was conducted on patients hospitalized in France for methadone poisoning (ICD-10: T40.3) between January 2014 and December 2020, using the database of the Programme de Médicalisation des Systèmes d'Information. An interrupted time series using the Unobserved Components Model was performed to predict the monthly incidence of MUHs in 2020 on the basis of previous years data and confronted to MUHs really observed. The characteristics of the patients (age, sex, comorbidities) and hospitalizations (regions, duration of hospitalization, co-consumptions) were described over four time-periods: before lockdown, first lockdown, after-first lockdown, second lockdown. Results: Compared to the predictions, higher incidence of MUHs was found during the first month of lockdown (March) (66 cases vs. 51.3; IC95%: 34–65) and a large increase during the month following the end of the first lockdown (June) (79 cases vs. 61; IC95%: 46–75). Psychiatric comorbidities, psycho-social difficulties and co-consumptions (alcohol, cannabis, cocaine) were more observed during first lockdown, whereas patients aged over 30 years old and from Nouvelle-Aquitaine, Occitanie and Bretagne were more concerned after. The second lockdown did not present any particularity. Discussion/Conclusion: First lockdown had a significant impact on the incidence of MUHs. These results converge with the data from the reinforced national monitoring showing that methadone was the first substance involved in overdoses and deaths during and after the first lockdown [1].< Réduire