Background and Objectives. Earlier studies of the use of articaine in intravenous regional anesthesia (IVRA) are conflicting. In fact, despite similar physicochemical properties and regional anesthetic action, significant differences between articaine and prilocaine in IVRA have been reported. Articaine, being a potent local anesthetic with low degree of toxicity and being rapidly metabolized by esterases, could be a useful local anesthetic particularly in IVRA and, perhaps, could challenge prilocaine, the present local anesthetic of choice for this technique. Methods. A double-blind, cross-over study of IVRA of the upper extremity in 10 healthy volunteers was performed. There was at least a 1-week interval between the use of the two anesthetics in each volunteer. After exsanguination with an Esmarch bandage, IVRA was induced either with preservative-free 0.5% articaine (5% Ultracaine, Hoechst, Germany, diluted with 0.9% NaCl) or 0.5% prilocaine (Citanest, Astra, Södertälje, Sweden) (35–50 mL, according to weight), injected in 2 minutes. Sensation at defined skin spots that were innervated by the median, musculocutaneous, radial, and ulnar nerves was tested by pinprick; motor function was tested by the movements of the wrist. After 20 minutes, the tourniquet cuff was deflated in one step. Circulatory, toxic, and skin reactions were registered. At least 1 week after the second IVRA intracutaneous allergy testing with 0.5% articaine, 0.5% prilocaine, histamine, and saline was performed. Results. There were no significant differences between the two local anesthetics in the onset of analgesia or anesthesia, degree of motor block, and recovery of IVRA. Onset of analgesia occurred 4.2–5.6 minutes, on average, after the injection. One volunteer had short-lasting tinnitus after tourniquet cuff deflation when prilocaine was used. Erythematous nonitching skin rashes developed in 8 of 10 volunteers when articaine was used, and two volunteers had rashes when prilocaine was used. These rashes disappeared within an hour, and negative intracutaneous test results confirmed their nonallergic origin. Conclusion. Both 0.5% articaine and 0.5% prilocaine, in a median dose of 40 mL in adults, injected in 2 minutes, are effective and equipotent local anesthetics in IVRA of the arm. An earlier reported four-time faster onset time of the block by articaine in comparison with prilocaine may be caused by a very rapid injection rate (40 mL/30 sec) by the investigators of that study. The erythematous skin rashes after IVRA, in particular when articaine was used, may be a sign of venous endothelial irritation.