While effective for acute pain control, recent pre-clinical evidence has raised concerns regarding an association between NSAIDs and chronic pain and potential opioid use. The objective of this paper was to explore the association between peri-operative use of prescription NSAIDs and the need for continued opioid prescriptions lasting 90–180 days in previously opioid-naïve patients undergoing total knee arthroplasty. Join Prof Ed Mariano and the authors to find out what the key messages are for clinicians.