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Exposure to opioid analgesics have historically raised concern for a risk of developing opioid use disorder. Prescriber audit-and-feedback interventions may reduce opioid prescribing, but some studies have shown detrimental effects for current users. We examined the effectiveness of an audit and feedback intervention, named Portrait, to reduce initiation of opioid analgesics among opioid-naïve patients experiencing pain. REDONNA was a single-blinded, two-arm (Early vs Delayed mailing) randomized trial of a portrait for eligible family physicians (FPs) in British Columbia (BC), Canada. The primary outcome was the change in the number of initiations of opioid analgesic prescriptions written by FPs for acute/chronic pain management. We compared outcomes for a 6-month window before vs. after each mailed intervention, using differences in percent differences (DPD) with 95% confidence intervals (CI) and odds ratios (OR) from logistic regressions adjusted for clustering of patients by FP. In the Early (n = 2260) and Delayed (n = 2156) groups, opioid initiations per month were the same in the Before (2.10 Early; 2.06 Delayed) and After (1.94 Early; 1.95 Delayed) windows. The DPD was −2.1% (CI: −4.4% to 0.3%), and ORs were: 0.98 (CI: 0.96 to 1.01) for any opioid, 0.97 (CI: 0.94 to 1.01) for codeine (62% of initiations), and 1.0 (CI: 0.97 to 1.07) for tramadol (25% of initiations). There were no differences in mean quantity of tablets, mean milligrams of morphine equivalents (MME), or mean number of days. Portrait had no impact on FPs' rates of prescribing opioid analgesics to opioid-naïve patients experiencing pain. The study was registered prospectively on 30 March 2020 at the ISRCTN Register (https://www.isrctn.com/ISRCTN34246811). [ABSTRACT FROM AUTHOR]