One hundred patients scheduled to undergo a primary total knee arthroplasty (TKA) were randomized to receive 2 weeks of daily 10 mg oral prednisone (n=50) or control (n=50) for post-surgical pain relief. Primary outcomes of interest included pain during rest and movement measured using the visual analogue scale (VAS), which were both evaluated up to 84 days post-TKA. Secondary outcomes of interest included daily usage of tramadol and celecoxib measured up to 84 days post-TKA. Also, incidence of complications was measured. Results revealed that VAS pain scores at rest were significantly lower at 14 and 28 days post-TKA (p<0.05 for both), and at 7 days, 14 days, and 28 days post-TKA for VAS pain during movement (p<0.05 for all) in the prednisone group vs. control. Tramadol usage per day was significantly lower in the prednisone group vs control at 7- and 14-days post-surgery (p=0.034 and p<0.01, respectively). Also, celecoxib usage per day was significantly reduced in the prednisone group compared to control at 14- and 28-days post-surgery (p<0.01 and p=0.024, respectively). No complications were observed in either group.