["Addiction, EarlyView. ", "\nAbstract\n\nAims\nTo examine the comparative effects of slow‐release oral morphine (SROM) vs. methadone for the treatment of opioid use disorder (OUD) on healthcare use.\n\n\nDesign\nThis retrospective cohort study emulated a target trial using electronic medical record data from Vancouver Coastal Health Authority linked with population‐based administrative health data from British Columbia (BC), Canada.\n\n\nSetting\nVancouver Coastal Health region in BC, between 1 July 2017 and 30 June 2024, operating under a universal healthcare system, where the majority of illicit opioids are contaminated with fentanyl.\n\n\nParticipants\nOUD patients aged between 18 and 65 years.\n\n\nInterventions\nIntent‐to‐treat (ITT): receiving a new prescription of SROM or methadone for the treatment of OUD (regardless of treatment initiation or adherence). Per‐protocol (PP): initiating and adhering to the prescribed SROM vs methadone (real‐world on‐treatment exposure).\n\n\nMeasurements\nThe daily rate of healthcare use—including all‐cause and opioid‐specific emergency department (ED) visits, all‐cause and opioid‐specific hospitalization days, all‐cause physician encounters/services, OUD‐related physician visits, and non‐OUD‐related primary care physician visits—over 1 year following treatment prescription or initiation was modelled using weighted modified Poisson regression with generalized estimating equations. Cumulative healthcare use at 1 year and corresponding adjusted rate ratios (aRRs) were estimated.\n\n\nFindings\nWe identified 3254 unique individuals [median (Q1–Q3) age 37 (30–46) years, 64.2% male] contributing to 4059 person‐trials (eligible treatment episodes) for the ITT analysis (32.6% SROM) and 1992 unique individuals contributing to 2276 person‐trials for the PP analysis (27.4% SROM). ITT analysis shows that receiving a SROM vs. methadone prescription was not associated with statistically significant differences in the rates of all‐cause [aRR = 1.10, 95% confidence interval (CI) = 0.997–1.20] and opioid‐specific ED visits (aRR = 1.00, 95% CI = 0.90–1.13), all‐cause (aRR = 0.99, 95% CI = 0.81–1.18) and opioid‐specific hospitalization days (aRR = 0.97, 95% CI = 0.78–1.20), all‐cause physician encounters/services (aRR = 1.00, 95% CI = 0.94–1.06), OUD‐related physician visits (aRR = 0.94, 95% CI = 0.87–1.01) and primary care physician visits (aRR = 1.11, 95% CI = 0.98–1.24). PP analysis also did not observe statistically significant differences across healthcare outcomes among those who initiated and remained on SROM vs. methadone treatment, with aRRs of 1.24 (95% CI = 0.91–1.50), 1.01 (95% CI = 0.67–1.36), 1.06 (95% CI = 0.65–1.58), 0.95 (95% CI = 0.53–1.58), 1.03 (95% CI = 0.90–1.17), 0.97 (95% CI = 0.82–1.14) and 1.06 (95% CI = 0.73–1.46), respectively.\n\n\nConclusions\nThis emulated trial on opioid use disorder patients under a universal healthcare setting in Canada did not observe statistically significant differences in risk of healthcare use outcomes between the patients receiving slow‐release oral morphine and those receiving methadone following treatment prescription and initiation. This supports slow‐release oral morphine as a viable alternative to methadone with similar real‐world effectiveness in preventing all‐cause and opioid‐related acute healthcare needs and the potential to expand treatment options for opioid use disorder without increasing health system burden.\n\n"]