Seventy patients with knee osteoarthritis undergoing total knee arthroplasty were randomized to receive either a periarticular infiltration of methylene blue combined cocktail (n=35) or a conventional cocktail alone (n=35). The primary outcome of interest was postoperative pain scores assessed by the Numeric Rating Scale (NRS). Secondary outcomes of interest included postoperative sufentanil consumption, inflammatory markers (IL-6 and CRP), and adverse events including wound healing and complications. Outcomes were assessed at 24, 48, and 72 hours, as well as at 7, 14, and 28 days postoperatively. Overall, the results of the study revealed that patients in the methylene blue group experienced significantly lower pain scores at all time points and reduced opioid use within the first 72 hours. There were also lower IL-6 levels without an increase in adverse events. The findings suggest that adding methylene blue to a periarticular cocktail can safely enhance analgesia and reduce inflammation following total knee arthroplasty.