Background: Oxycodone is increasingly prescribed for postpartum analgesia in lieu of codeine owing to concerns regarding the neonatal safety of codeine during lactation. We examined whether initiation of oxycodone after delivery was associated with an increased risk of persistent opioid use relative to initiation of codeine., Methods: We conducted a population-based cohort study of people who filled a prescription for either codeine or oxycodone within 7 days of discharge from hospital after delivery between Sept. 1, 2012, and June 30, 2020. The primary outcome was persistent opioid use, defined as 1 or more additional prescriptions for an opioid within 90 days of the first postpartum prescription and 1 or more additional prescriptions in the 91 to 365 days thereafter. We used inverse probability of treatment weighting to assess the risk of persistent postpartum opioid use, comparing people who initiated oxycodone with those who initiated codeine., Results: Over the 8-year study period, we identified 70 607 people who filled an opioid prescription within 7 days of discharge from hospital: 21 308 (30.2%) received codeine and 49 299 (69.8%) oxycodone. Compared with people who filled a prescription for codeine, receipt of oxycodone was not associated with persistent opioid use (relative risk [RR] 1.04, 95% confidence interval [CI] 0.91-1.20). We found an association between a prescription for oxycodone and persistent use after vaginal delivery (RR 1.63, 95% CI 1.31-2.03), but not after cesarean delivery (RR 0.85, 95% CI 0.73-1.00)., Interpretation: Initiation of oxycodone (v. codeine) was not associated with an increased risk of persistent opioid use, except after vaginal delivery., Competing Interests: Competing interests: Jonathan Zipursky has received payments from private law firms for medicolegal opinions on the safety and effectiveness of analgesics, including opioids. Dr. Zipursky is supported by the University of Toronto Department of Medicine Clinician Scientist Training Program and a Canadian Institutes of Health Research (CIHR) Banting and Best Doctoral Award. David Juurlink reports receiving payment for expert testimony from multiple law firms related to analgesics, including opioids; an honorarium for a lecture on pain management from Texas Tech University Health Sciences Center; and reimbursement for travel costs for presentations and scientific meetings from CIHR, Stanford University and Texas Tech University Health Sciences Center. Dr. Juurlink is an unpaid member of Physicians for Responsible Opioid Prescribing (PROP), a nongovernmental organization with the goal of promoting opioid stewardship. Tara Gomes reports receiving grant and contract funding from the Ontario Ministry of Health, the Public Health Agency of Canada, the Ontario College of Pharmacists and the Government of Canada (paid to institution in support of Dr. Gomes’ research program). A Tier 2 Canada Research Chair supports Dr. Gomes’ salary. Dr. Gomes has also received payment for travel and a stipend for participating in the Drugs and Therapeutics Advisory Committee from Indigenous Services Canada. Muhammad Mamdani reports receiving grant funding from Roche, examining drug use for multiple sclerosis. Dr. Mamdani has also received honoraria as a member of the scientific advisory board of SaNotize. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)