SummaryOpioids are often used to provide postsurgical analgesia but may cause harm if used inappropriately. We introduced an opioid stewardship program in three Melbourne hospitals to reduce the inappropriate use of opioids after patient discharge. The program had four pillars: prescriber education, patient education, a standardised quantity of discharge opioids, and general practitioner (GP) communication. Following introduction of the program, we undertook this prospective cohort study. The study aimed to describe post-program discharge opioid prescribing, patient opioid use and handling, and the impact of patient demographics, pain and surgical treatment factors on discharge prescribing. We also evaluated compliance with the program components. We recruited 884 surgical patients from the three hospitals during the ten-week study period. Discharge opioids were dispensed to 604 (74%) patients, with 20% receiving slow-release opioids. Junior medical staff undertook 95% of discharge opioid prescribing, which was guideline-compliant for 78% of patients. Of the patients discharged with opioids, a GP letter was sent for only 17%. Follow-up at two weeks was successful in 423 (70%) patients and in 404 (67%) at three months. At the three-month follow-up, 9.7% of patients reported ongoing opioid use; in preoperatively opioid naïve patients, the incidence was 5.5%. At the two-week follow-up, only 5% reported disposal of excess opioids, increasing to 26% at three months. Ongoing opioid therapy at three months in our study cohort (9.7%; 39/404) was associated with preoperative opioid consumption and higher pain scores at the three-month follow-up. The introduction of the opioid stewardship program resulted in highly guideline-compliant prescribing, but hospital-to-GP communication was uncommon and opioid disposal rates were low. Our findings suggest that opioid stewardship programs can improve postoperative opioid prescribing, use and handling, but the realisation of these gains will require effective program implementation.