Objective <p>The aim of this study was to comprehensively investigate the clinical efficacy of intraoperative local joint injection and intramuscular injection of betamethasone in patients with severe traumatic knee osteoarthritis (KOA).</p> Methods <p>80 patients with severe traumatic KOA undergoing total knee arthroplasty were retrospectively recruited and rolled into S1 group (intra-articular injection of ropivacaine + betamethasone and isotonic saline mixture at joint incision), S2 group (muscle local injection of betamethasone before incision closure, simultaneously intra-articular injection of ropivacaine + isotonic saline mixture at joint incision), and D group (intra-articular injection of ropivacaine + isotonic saline mixture at the joint incision). Visual analog scale (VAS) score, serum inflammatory factors (IFs), hospital for special surgery (HSS)score, Pittsburgh sleep quality index (PSQI), and adverse reaction events (AREs) were analyzed.</p> Results <p>Pain scores of patients in all three groups decreased drastically over time on postoperative days (PDs) 1, 2, and 3, with the scores in S1 and S2 groups markedly inferior to D group (<i>P</i> &lt; 0.05). HSS scores of patients in S1 and S2 groups at postoperative months 1, 3, and 6 were considerably superior to those in D group (<i>P</i> &lt; 0.05). PSQI scores of patients in S1 and S2 groups at postoperative months 1, 3, and 6 were notably inferior to those in D group (<i>P</i> &lt; 0.05).</p> Conclusion <p>Both intraoperative local joint injection and muscle injection of betamethasone are effective in patients with severe traumatic KOA.</p>