Background: Total knee arthroplasty (TKA) is associated with moderate-to-severe postoperative pain despite multimodal opioid-sparing analgesia. Pain catastrophising or preoperative opioid therapy is associated with increased postoperative pain. Preoperative glucocorticoid improves pain after TKA, but dose-finding studies and benefit in high pain responders are lacking. Methods: A randomised double-blind controlled trial with preoperative high-dose intravenous dexamethasone 1 mg kg⁻¹ or intermediate-dose dexamethasone 0.3 mg kg⁻¹ in 88 patients undergoing TKA with preoperative pain catastrophising score >20 or regular opioid use was designed. The primary outcome was the proportion of patients experiencing moderate-to-severe pain (VAS >30) during a 5 m walk 24 h postoperatively. Secondary outcomes included pain at rest during nights and at passive leg raise, C-reactive protein, opioid use, quality of sleep, Quality of Recovery-15 and Opioid-Related Symptom Distress Scale, readmission, and complications. Results: Moderate-to-severe pain when walking 24 h postoperatively was reduced (high dose vs intermediate dose, 49% vs 79%; P<0.01), along with pain at leg raise at 24 and 48 h (14% vs 29%, P=0.02 and 12% vs 31%, P=0.03, respectively). C-reactive protein was reduced in the high-dose group at both 24 and 48 h (both P<0.01). Quality of Recovery-15 was also improved (P<0.01). Conclusions: When compared with preoperative dexamethasone 0.3 mg kg⁻¹ i.v., dexamethasone 1 mg kg⁻¹ reduced moderate-to-severe pain 24 h after TKA and improved recovery in high pain responders without apparent side-effects. Clinical trial registration: NCT03763734.