Codeine is the most used opioid globally. In December 2016, Australia announced that low-strength codeine (≤15 mg) would be re-scheduled and no longer available for purchase over-the-counter; this was implemented in February 2018. We aimed to evaluate the effect of this scheduling change on codeine misuse and use, and misuse of other opioids.Interrupted time series analysis of monthly opioid exposure calls to New South Wales Poisons Information Centre (NSWPIC, captures 50% of Australia's poisoning calls), January 2015 - January 2019, and monthly national codeine sales, March 2015 - March 2019. We incorporated a washout period (January 2017 - January 2018) between the announcement and implementation, when prescriber/consumer behaviour may have been influenced.Intentional opioid overdoses resulting in a call to NSWPIC.We used linear segmented regression to identify abrupt changes in level and slope of fitted lines. Codeine poisonings and sales were stratified into high-strength (>15 mg per dose unit) and low-strength (≤15 mg). Only low-strength formulations were re-scheduled.We observed an abrupt -50.8 percentage (95%CI: -79.0 to -22.6%) level change in monthly codeine-related poisonings and no change in slope in the 12 months after February 2018. There was no increase in calls to the NSWPIC for high-strength products, level change: -37.2% (95%CI: -82.3% to 8%), or non-codeine opioids, level change: -4.4% (95%CI: -33.3% to 24.4%). Overall, the re-scheduling resulted in a level change in opioid calls of -35.8% calls/month (95%CI: -51.2% to -20.4%). Low-strength codeine sales decreased by 87.3% (95%CI: -88.5 to -85.9%), with no increase in high-strength codeine sales in the 14 months following re-scheduling, -4.0% (95%CI: -19.6% to 14.6%).Codeine re-scheduling in Australia appears to have reduced codeine misuse and sales.