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Giorgio Ranieri,1 Bruno Violante,2 Federico Tamburi,3 Dario Cirillo,4 Antonio Coviello4,5 1Complex Operational Unit of Anesthesia and Operating Units, Department of Emergency and Internal Medicine, Isola Tiberina Hospital - Gemelli Isola, Rome, Italy; 2Complex Operational Unit of Prosthetic Surgery and Traumatology, Isola Tiberina Hospital - Gemelli Isola, Rome, Italy; 3Department of Anesthesia and Intensive Care Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Del Sacro Cuore, Rome, Italy; 4Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples “federico II”, Naples, Italy; 5Department of Life Sciences, Health and Health Professions, Link Campus University, Rome, ItalyCorrespondence: Dario Cirillo, Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples “Federico II”, Naples, Italy, Tel +39 3497013533, Fax +39 0817462281, Email dariocirillo3@gmail.comAbstract: Effective perioperative pain control is essential in Total Knee Arthroplasty (TKA) to support early mobilization and enhance recovery, particularly within Enhanced Recovery After Surgery (ERAS) protocols. The use of a thigh tourniquet, although common, is increasingly questioned due to its association with postoperative pain and thromboembolic risk, especially in patients with a history of Deep Vein Thrombosis (DVT). Periarticular Vasoconstrictor Infiltration (PVI) is a recently described technique aimed at achieving localized hemostasis through epinephrine-based infiltration. This case report illustrates the clinical utility of ultrasound-guided PVI as part of a multimodal, tourniquet-free strategy in high-risk patient. A 66-year-old female with severe right knee osteoarthritis and a history of right lower limb DVT underwent primary TKA under spinal anesthesia. Due to the patient’s elevated thrombotic risk—defined by a high Caprini score—a tailored regional anesthesia protocol was adopted, combining multi-target PVI with a proximal adductor canal block and spinal anesthesia. The PVI solution included ropivacaine, dexmedetomidine, and epinephrine. No tourniquet was inflated during the procedure. The surgical field remained bloodless throughout the 72-minute procedure. Intraoperative blood loss was less than 200 mL, and no transfusion was required. Postoperative analgesia was effective, opioid use was minimized, and the patient mobilized the same evening without complications. No clinical or ultrasound signs of early postoperative thrombotic events were observed. This case demonstrates the feasibility and clinical benefit of integrating ultrasound-guided PVI into a multimodal, tourniquet-free anesthetic strategy for TKA in high-thrombotic-risk patients. The approach provided effective analgesia and hemostasis, aligned with ERAS principles, and may represent a valuable alternative for personalized perioperative care in orthopedic surgery.Keywords: total knee arthroplasty, TKA, free-tourniquet, periarticular vasoconstrictor infiltration, case report, nerve block