Purpose <p>This study aimed to evaluate the association of oxidized regenerated cellulose (ORC) powder in perioperative blood management during total knee arthroplasty (TKA) using a subvastus approach with limited tourniquet use.</p> Methods <p>We retrospectively analyzed 140 patients who underwent primary TKA using the subvastus approach at our institution between January 2023 and December 2025. The Patients were divided into ORC (n = 69) and non-ORC (n = 71) groups based on the intraoperative application of ORC powder. All patients received local tranexamic acid (TXA), and the tourniquets were inflated only during cementation. To account for potential confounding, multivariable linear regression analysis was performed. The primary outcomes were estimated total blood loss (eTBL) and hidden blood loss (HBL). Secondary outcomes included postoperative pain (numeric rating scale, NRS) and the incidence of postoperative complications.</p> Results <p>The ORC group demonstrated significantly lower eTBL (599.2 ± 211.9 vs. 713.4 ± 273.3&#xa0;mL, p = 0.007) and HBL (398.3 ± 207.6 vs. 485.8 ± 273.0&#xa0;mL, p = 0.03) compared to the non-ORC group. Multivariable analysis confirmed that ORC use was independently associated with lower eTBL (β = -117.2; p = 0.009) and HBL (p = 0.02), though it was not an independent predictor for pain reduction on postoperative day seven (p = 0.15). There were no significant differences in operative time, or the incidence of postoperative complications.</p> Conclusion <p>The adjunctive use of ORC powder during TKA was associated with lower eTBL and HBL.</p>