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Aims: In March 2020, British Columbia issued Risk Mitigation Guidance (RMG) to support prescribing of pharmaceutical alternatives to illicit drugs, in order to reduce risk for COVID-19, overdose, and withdrawal among people who use drugs. This study evaluated factors associated with 60-day adherence to novel opioid alternatives prescribed at an inner-city health centre in Victoria, Canada., Methods: A chart review was conducted to collect data on sociodemographic information, medical histories, and follow-up services among all clients prescribed novel opioid alternatives from March 2020-August 2020 (n = 286). Bivariable and multivariable regression were used to identify independent and adjusted factors associated with 60-day adherence., Results: Overall, 77% of 286 clients were still receiving opioids after 60 days of follow-up. Medications included hydromorphone (n = 274), sustained-release oral morphine (n = 2), and oxycodone (n = 9). The adjusted odds of 60-day adherence to novel opioid alternatives were significantly higher for those receiving a mental health medication (aOR = 3.49, 95%CI = 1.26, 11.00), a higher maximum daily dosage of RMG prescriptions (aOR = 1.03 per mg increase, 95%CI = 1.01, 1.04), and those with continuous receipt of OAT (aOR = 6.25, 95%CI = 2.67, 15.90)., Conclusions: Higher dosages and co-prescription of mental health medications and OAT may help support better adherence to this form of prescriber-based "safer supply". Further work is needed to identify optimal prescribing practices and the longer term impacts of differing implementation scenarios., Competing Interests: Declarations of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)