Introduction Opioid prescribing is increasing in many countries. In Australia, there is limited research on patterns of prescribing and access, or the outcomes associated with this use. The aim of this research programme is to use national dispensing data to estimate opioid use and costs, including problematic or extramedical use in the Australian population. Methods and analysis In a cohort of persons dispensed at least one opioid in 2013, we will estimate monthly utilisation and costs of prescribed opioids, overall and according to individual opioid formulations and strengths. In a cohort of new opioid users, commencing therapy between 1 July 2009 and 31 December 2013, we will examine patterns of opioid use including initiation of therapy, duration of treatment and concomitant use of opioids and other prescribed medicines. We will also examine patterns of extramedical opioid use based on indicators including excess dosing, use of more than one opioid concomitantly, doctor/pharmacy shopping and accelerated time to prescription refill. Ethics and dissemination This protocol was approved by the NSW Population and Health Services Ethics Committee (March 2014) and data access approved by the Department of Human Services External Review Evaluation Committee (June 2014). This will be one of the first comprehensive Australian studies with the capability to investigate individual patterns of use and track extramedical use. In the first instance our analysis will be based on 5 years of dispensing data but will be expanded with ongoing annual data updates. This research has the capability to contribute significantly to pharmaceutical policy within Australia and globally. In particular, the trajectory of extramedical prescription-opioid use has been the subject of limited research to date. The results of this research will be published widely in general medical, pharmacoepidemiology, addiction and psychiatry journals.