Background: Guidelines for acute postoperative pain management recommend administering analgesics in multimodal combination to facilitate synergistic benefit, reduce opioid requirements and decrease side-effects. However, limited observational research has examined the extent to which multimodal analgesics are prescribed and administered postoperatively following joint replacement. Methods: In this longitudinal study, we used three-point prevalence surveys to observe the 6-year trends in prescribing and use of multimodal analgesics on the orthopaedic wards of a single Australian private hospital. We collected baseline postoperative data from total hip and knee arthroplasty patients in May/June 2010 (Time 1, n = 86), and follow-up data at 1 year (Time 2, n = 199) and 5 years (Time 3, n = 188). During the follow-up, data on prescribing practices were presented to anaesthetists. Results: We found a statistically significant increase in the prescribing (p < 0.001) and use (p < 0.001) of multimodal analgesics over time. The use of multimodal analgesics was associated with lower rest pain (p = 0.027) and clinically significant reduction in interference with activities (p < 0.001) and sleep (p < 0.001). However, dynamic pain was high and rescue opioids were likely under-administered at all time points. Furthermore, while patients reported high levels of side-effects, use of adjuvant medications was low. Conclusions: We observed significant practice change in inpatient analgesic prescribing in favour of multimodal analgesia, in keeping with contemporary recommendations. Surveys, however, appeared to identify a clinical gap in the bedside assessment and management of breakthrough pain and medication side-effects, requiring additional targeted interventions. Significance: Evaluation of 6-year trends in a large Australian metropolitan private hospital indicated substantial growth in postoperative multimodal analgesic prescribing. In the context of growing global awareness concerning multimodal analgesia, findings suggested diffusion of best-evidence prescribing into clinical practice. Findings indicated the effects of postoperative multimodal analgesia in real-world 108 | KHAW et Al. How to cite this article: Khaw D, Bucknall T, Considine J, et al. Six-year trends in postoperative prescribing and use of multimodal analgesics following total hip and knee arthroplasty: A single-site observational study of pain management.