To characterise the trajectory in the years leading up to 2018 in pharmaceutical-opioid and heroin morbidity in Victoria, Australia, and to assess the effect on that trajectory of reformulation of oxycodone to a form that could not be easily snorted or injected.Interrupted time series analyses of population-level data before versus after reformulation of oxycodone, stratified by sex.Victoria, Australia.The population of Victoria aged 12+ years.Ambulance patient care and Emergency Department (ED) records were examined using both fixed-code and free-text fields, with each record manually cleaned and checked by trained coders. These were used to derive the output variables providing an index of harm: rates of opioid-related ambulance attendances and emergency department (ED) attendances for pharmaceutical opioids and heroin. The input variable was pre- versus post oxycodone reformulation.There were 30,045 (58% male) opioid-related ambulance attendances from January 2012-October 2018, and 10,113 (51% male) ED attendances from July 2008-June 2018. There was an increase in the rate (events per 100,000 persons per year) of all-opioid ED attendances from 2008-2018 (increase: 0.063; 95% CI: 0.049,0.078). Pharmaceutical-opioid ED attendances decreased from 2014 onwards (slope change:-0.083; 95%CI:-0.108,-0.059). Heroin-related ED attendances increased from 2014 to 2018; 11,324 heroin-related ambulance attendances and 1,980 ED attendances were observed from April 2014 to June 2018, compared with the respective estimates of 8,176 and 1,661 had the pre-April 2014 trend continued (ambulance slope change:0.296, 95%CI:0.104,0.489; ED slope change:0.026, 95% CI:0.005,0.046). The inflection point of 2014 coincided with the reformulation of oxycodone.In Victoria, Australia, there appears to have been a trend starting around mid-2014 of increasing heroin-related harm, and a flattening of the increase or a decrease of harms relating to pharmaceutical opioids. These changes may in part reflect reformulation of oxycodone to reduce the extent to which it can be injected or snorted.