Our aim was to determine the frequency and characteristics of post-surgery prescription of opioid medication and to describe patients’ handling of discharge opioid medications. We performed a multicentre prospective cohort study of adult patients undergoing elective or emergency surgery with a postoperative stay of one or more nights, with phone follow-up at two weeks after hospital discharge. The main outcome measures included the proportion of patients prescribed discharge opioid medications, post-discharge opioid use, opioid storage and disposal. Of the 1450 eligible surgical patients, opioids were dispensed on discharge to 858 (59%, 95% confidence interval (CI) (57%–62%)), with immediate-release oxycodone the most common medication. Of the 581 patients who were discharged with opioid medication and completed follow-up, 27% were still requiring opioids two weeks after discharge. Post-discharge opioid consumption was highly variable in the study cohort. The majority (70%) of patients had leftover opioids and only a small proportion (5%) reported disposal of the surplus. In a multivariate model, patients with characteristics of age 45 years or less (odds ratio, OR = 1.78, 95% CI (1.36–2.33) versus older than 45 years), American Society of Anesthesiologists’ physical status (ASA) scores of 1 or 2 (OR = 1.96, 95% CI (1.52–2.53) versus ASA score 3 to 5), higher anticipated surgical pain (OR = 1.45, 95% CI (1.08–1.94) severe versus moderate, OR = 17.48, 95% CI (5.79–52.69) severe versus nil/mild) and public funding status (OR = 1.89, 95% CI (1.36–2.64) versus other) were more likely ( P < 0.001) to receive discharge opioids. Post-surgery prescription of opioids is common and supply is often excessive. Post-discharge opioid handling included suboptimal storage and disposal.