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We use a rigorous LTOT definition to examine risk of opioid overdose by duration of treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data were from a large private health insurance provider in North Carolina linked to mortality records from 2006\u20132018. Eligible patients were adults (18\u201364) newly initiating opioid therapy after a pain diagnosis or surgery. We defined LTOT as \u2265\u20091 opioid prescription per month totaling \u2265 60\u2009days' supply within 90\u2009days. We used inverse probability (IP)\u2010weighted cumulative incidence functions to estimate three\u2010year risk of opioid overdose and IP\u2010weighted Fine\u2013Gray models to estimate sub\u2010distribution hazard ratios, comparing LTOT to short\u2010 to medium\u2010term opioid therapy (SMTOT). We also examined modification by derived indication of acute pain or surgery versus chronic pain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 491\u2009369 patients, and 1.7% were exposed to LTOT. The three\u2010year risk of opioid overdose was 0.3 percentage points (RD<jats:sub>w<\/jats:sub>\u2009=\u20090.003, 95% CI: 0.001, 0.005) higher in LTOT patients compared to patients with SMTOT. The weighted hazard of opioid overdose was 4.4 times as high (HR<jats:sub>w<\/jats:sub> 4.42, 95% CI 2.41, 8.11) among patients exposed to LTOT versus SMTOT. We did not find meaningful modification by clinical indication for opioid therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Exposure to LTOT was associated with increased risk of opioid overdose in this population of privately insured patients using a rigorous definition of LTOT. These findings confirm the importance of guidelines to minimize duration of opioid therapy whenever possible.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.70090","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T03:53:52Z","timestamp":1736826832000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Long\u2010Term Opioid Therapy and Risk of Opioid Overdose by Derived Clinical Indication in North Carolina, 2006\u20132018"],"prefix":"10.1002","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1298-4433","authenticated-orcid":false,"given":"Bethany L.","family":"DiPrete","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Gillings School of Global Public Health University of North Carolina  Chapel Hill 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North Carolina  Chapel Hill USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul L.","family":"Delamater","sequence":"additional","affiliation":[{"name":"Carolina Population Center University of North Carolina  North USA"},{"name":"Department of Geography University of North Carolina  North USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Fulcher","sequence":"additional","affiliation":[{"name":"Injury Prevention Research Center University of North Carolina  Chapel Hill USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian W.","family":"Pence","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Gillings School of Global Public Health University of North Carolina  Chapel Hill 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