Background: Medication incidents in hospitals are common and occur at all phases of the medication management cycle. Clinical incidents for high-risk medications such as opioids have the potential to cause significant harm, yet opioid incidents are an under researched area of health service safety and quality. Aim: The aim of this study was to identify opioid medication safety incident types, occurrence in the medication management cycle, causative factors and level of patient harm to inform clinical care. Method: A multi-methods analysis of all reported opioid-related medication incidents, in all 93 Western Australian (WA) public hospitals, between 1 July 2017 and 30 June 2018 was conducted. Results: Opioid medications as a class were implicated in 11.0% (857) of all medication-related clinical incidents reported in 2017–18, with tapentadol, a relatively new opioid, the most reported (131; 15.3%). No reported incidents resulted in death, however, 0.5% (4) caused severe harm and 3.5% (30) caused moderate harm. The majority of incidents occurred during the administration phase of the medication management cycle (630; 73.5%). ‘Incorrect dose’ (146; 17%) followed by ‘omission of dose’ (116; 13.5%) were the most frequent incident types reported. ‘Not checking properly’ (554; 64.6%) followed by ‘not following procedures’ (167; 19.5%) were the most frequent causative factors. Conclusion: Vigilance in identifying, reporting and reviewing opioid medication safety incidents and causative factors are imperative to mitigating errors and preventing patient harm. Study findings should be used to develop targeted strategies to reduce opioid incidents in public hospitals.