Introduction: As soon as the lockdown began, during the COVID-19 pandemic, first cases of overdoses were reported with opioids and cocaine to the French Addictovigilance Network [1]. However, little information was available on substance use-related hospitalizations (H-SPA). The objective of this study was to describe changes in the relative incidence of H-SPA before, during, and after the lockdown, and to describe the characteristics of hospitalizations and patients. Material and methods: This retrospective study was conducted on patients hospitalized at a University Hospital from January to July 2020 in the context of use of methadone, buprenorphine, benzodiazepines, heroin, morphine, codeine, cocaine, ecstasy, and alcohol, using the database of the Programme de medicalisation des systèmes d'information. Three time periods were defined for the analysis: before (01/01–16/03), during (17/03–10/05), and after the lockdown (11/05–31/07). These results were compared to the average of the data analyzed between 2017 and 2019 at the same three time periods. Results: In this study, 5,674 patients and 6,135 stays were included. H-SPA had decreased by 24% during the year of the pandemic, in particular during lockdown with a 57.6% decrease compared to previous years. In contrast, methadone was associated with a 233.3% increase in post-lockdown hospitalizations compared to 2017. Among patients hospitalized after methadone use, 4 had no known history of opiate use, 6 were known opiate/methadone users without methadone treatment, 7 were being treated with methadone. In 2020, H-SPA were more severe and involved drug-using patients with cardiovascular disease. Methadone/cocaine association was reported in 1/4 of deaths during the lockdown. Discussion/Conclusion: During the year of the pandemic and especially during the lockdown, H-SPA decreased but were more severe. Severe H-SPA were more likely to occur in drug-using patients with cardiovascular disease. This study highlights also a strong increase of hospitalizations related to methadone consumption (in opioid-naive subjects, or not) since the lockdown.Read less <