Opioid treatment in postoperative pain management is crucial, but the impact of administration practices on outcomes is unclear. The hypothesis was that prescription trends remained stable over recent years, and that no difference in mortality and readmission risks is associated with prescription strategies. Electronic health records of surgical episodes in the Capital and Zealand Regions of Denmark from 2017 to 2021 were analysed. All opioids administered during postoperative admission were converted to oral morphine equivalents (OMEQs) and an average daily dose per patient was calculated. The opioid administered in the highest OMEQ dosages is considered the primary opioid strategy for the surgical case. Administration trends were analysed through linear regression, and Cox regression was used to calculate hazard ratios to assess dominant opioid strategies' association with 90-day mortality and readmission rates while controlling for confounders. A total of 183 317 patients met the inclusion criteria. Prescription trends remained steady during the study period. Multivariable analysis revealed increased readmission risk (HR 1.18, P < 0.001) of tramadol and tapentadol compared to morphine. They exhibited decreased 90-day mortality risk (HR 0.63, P < 0.001). Oxycodone had similar readmission risk (HR 1.009, P = 0.24) but lower 90-day mortality risk (HR 0.68, P < 0.001). Postoperative in-hospital opioid administration remained stable from 2017 to 2021. Tramadol/tapentadol had a higher risk of readmission but lower mortality risk. Oxycodone had comparable readmission but reduced mortality risk. This study provides a framework for future clinical trials assessing this potential impact of opioids in a targeted manner.