Background: Ambulatory Muller phlebectomy for varicose veins can be performed under local anesthesia. However, subcutaneous injection of local tumescent anesthetics may cause discomfort because of acidity of the solution. Addition of sodium bicarbonate lowers the acidity of anesthetic solutions, which might cause less pain. The objective of this study was to study whether alkalinization of the local anesthetic solution with sodium bicarbonate 1.4% decreases perioperative pain during Muller phlebectomies. Methods: It is a double-blind single-center randomized controlled trial. In all, 101 patients scheduled for ambulatory Muller phlebectomy were randomized to receive either local anesthesia with alkalinized solution (lidocaine 1% and epinephrine in sodium bicarbonate 1.4%) or standard solution (lidocaine 1% and epinephrine in saline 0.9%). Primary outcome was pain during injection of local anesthetics with the use of the Visual Analogue Scale (VAS). Secondary outcomes were peroperative and postoperative pain, use of analgesics, patient satisfaction, return to function, and complications. Results: Patients receiving subcutaneous injection of local anesthetics diluted in sodium bicarbonate 1.4% experienced significantly less pain during injection compared with patients treated with standard anesthetic solution (VAS, 1.75 +/- 1.8 vs. 3.55 +/- 2.2, P <0.00). Peroperative and postoperative pain, complication rates, use of analgesics, patient satisfaction, return to function, and complications did not differ between the 2 groups (P > 0.10). Conclusions: Alkalinization of local anesthetic solution with sodium bicarbonate 1.4% significantly improves patient comfort during injection of local tumescent anesthesia.