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The COVID-19 pandemic led to disruptions in healthcare delivery, including postponement of elective procedures and difficulty accessing in-person care, which may have increased the need for strong pharmacological pain relief in some patients. With NHS England approval, we used routine clinical data from >20 million general practice adult patients in OpenSAFELY-TPP. We used interrupted time series analysis to quantify trends in prevalent and incident opioid prescribing prior to the pandemic (January 2018-February 2020) and changes during the COVID-19 lockdown period (March 2020-March 2021) and recovery period (April 2021-June 2022). We identified how these changes varied in people living in care homes, and by age, sex, deprivation, ethnicity, and geographic region. The median number of people prescribed an opioid per month was 50.9 per 1000 patients prior to the pandemic. We observed little change in overall prescribing after the start of the pandemic, except for a temporary increase in March 2020. There was a 9.8% (95%CI -14.5%, -6.5%) reduction in new opioid prescribing from March 2020, sustained to the end of the study period. Reductions in new prescribing were observed for all demographics except people 80+ years. Among care home residents, in April 2020 new opioid prescribing increased by 112.5% (95%CI 92.2%, 134.9%) and parenteral opioid prescribing increased by 186.3% (95%CI 153.1%, 223.9%). Changes in opioid prescribing during the COVID-19 pandemic were mostly consistent across subgroups with the exception of differences by age and care home …