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Objective: The objective of this study was to compare the efficacy of intradermal lidocaine anesthesia by two jet injectors to the routine needle infiltration and to the topical EMLA cream., Subjects and Methods: In a randomized, prospective, controlled trial, 100 consenting surgicenter patients in a university hospital setting were divided into four groups (n = 25, each); intradermal lidocaine anesthesia was given either by the conventional 25 g needle/syringe or the Med-E-Jet or Biojector injector or EMLA cream was applied on the skin. Visual analogue pain scores (VAS) or verbal pain intensity scores (PIS) were reported by the patients at lidocaine application and i.v. catheterization. Cost was also assessed., Results: At lidocaine application, no pain was reported, since proportions of VAS = 0 were 25/25 (CI: 0.868, 0.999) with Med-E-Jet; 24/25 (0.804, 0.991) with Biojector; 25/25 (0.868, 0.999) with EMLA; in contrast to pain, 3/25 (0.044, 0.302) with the needle (PP > 0.999). The VAS scores (mean +/- SD) were 0.00 +/- 0.00, 0.04 +/- 0.20, 0.00 +/- 0.00, and 2.4 +/- 2.2 respectively (p < 0.00 1). No pain was reported by proportions of PIS = 0 with Med-E-Jet: 25/25 (CI: 0.868, 0.999); with Biojector: 23/25 (0.749, 0.976); EMLA 25/25 (0,868, 0.999); but pain with the needle: 5/25 (0.090, 0.394) (PP > 0.999). The mean +/- SD PIS scores were 0.00 +/- 0.00, 0.16 +/- 0.55, 0.00 +/- 0.00, and 1.24 +/- 1.00, respectively (p < 0.001). At i.v. catheterization, the proportions of VAS = 0 scores were 22/25 with Med-E-Jet (0.698, 0.956); 21/25 (0.651, 0.934) with Biojector; but some pain with needle: 6/25 (0.116, 0.436) (PP > 0.999). The mean +/- SD VAS scores were: 0.12 +/- 0.33, 0.44 +/- 0.20, and 1.64 +/- 1.50, respectively (p < 0.001). No pain was reported by PIS = 0 scores in 24/25 (0.804, 0.991) with Med-E-Jet; 24/25 (0.804, 0.991) with the Biojector; but pain by zero PIS scores 13/25 (0.334, 0.703) in half of the patients in the needle group (PP > 0.999). The mean +/- SD scores were 0.00 +/- 0.00, 0.00 +/- 0.00, and 0.76 +/- 0.88, respectively (p < 0.001). The EMLA cream was not evaluated because of inadequate duration of application prior to anesthetic induction. Cost/application were: Med-E-Jet = $ 0.13; needle = $ 0.50; Biojector = $ 0.94 and EMLA = $ 3.76., Conclusion: Almost completely painless i.v. catheterization by jet injection of lidocaine was accomplished, while needle infiltration produced pain/discomfort and did not significantly reduce it at the i.v. needle insertion.