INTRODUCTION: Prolonged tourniquet inflation during surgery frequently leads to tourniquet hypertension (TH), which is thought to arise from compression of A-δ fibers leading to sympathetically mediated C fiber activation. In the lower extremity, C fibers and other sympathetic nerve fibers are carried along the femoral artery. We hypothesized that blockade of these fibers at the femoral artery would decrease the incidence of TH. METHODS: Thirty American Society of Anesthesia 1-3 patients aged 18-75 undergoing total ankle arthroplasty were randomized to receive 15 mL of injectate (mepivacaine 1.5% or saline placebo) at the anteromedial aspect of the common femoral artery at the level of the inguinal crease under ultrasound guidance. Both groups received preoperative popliteal sciatic and saphenous nerve blocks for analgesia and a standardized general anesthetic. Esmolol was administered if systolic blood pressure rose >30% above baseline. Incidence of TH was the primary outcome. RESULTS: TH was present in 93.3% of sham patients versus 33.3% of block patients. Mean systolic pressure at 120 min and 150 min of tourniquet time was significantly higher in the sham group compared with the block group. Esmolol requirement (95.3+107.6 v 8.0+14.2, p=<0.001) was also significantly higher in the sham group. No differences were noted in pain scores or opioid consumption, and no patient experienced sensory or motor block of the femoral nerve. DISCUSSION: Under these experimental conditions, injection of local anesthetic around the femoral artery reduced the incidence of TH and intraoperative esmolol requirement. TRIAL REGISTRATION NUMBER: www.clinicaltrials.gov (NCT03390426; December 28, 2017).