INTRODUCTION: Although venous cannulation is imperative during perioperative period, it inevitably causes venipuncture pain. Eutectic mixture local anesthetics (EMLA) has been used to reduce this pain, and various studies have been conducted to evaluate the efficacy of EMLA. But these studies did not elucidate the effect of EMLA exactly, because there were large individual differences in pain sensitivity. The aim of this study is to accurately evaluate the efficacy of EMLA cream for venipuncture pain relief compared with lidocaine tape in the same patients. METHODS: Participants were randomly allocated into EL or LE group. Participants received EMLA cream at one side dorsum of hand and lidocaine tape at another dorsum of hand before entering operation room. Local anesthetics were strictly applied according to their manufacturers' instruments, respectively. In the EL group, participants received venipuncture at EMLA cream site firstly. In LE group, participants, conversely, received venipuncture at lidocaine tape site firstly. Before anesthetic induction, local anesthetics were removed followed by venous cannulations. After cannulation, participants evaluated the pain by visual analog scale (VAS) and verbal rating scale (VRS).The primary outcome was VAS, and the secondary outcome was VRS. RESULTS: Data from 24 patients were analyzed. The VAS of EMLA cream was significantly lower than that of lidocaine tape (4 [0-18] vs 17 [8-45], p = 0.001, 95% CI - 25 to - 6). The VRS of EMLA cream was also significantly lower than that of lidocaine tape (2 [1-2] vs 2 [2-3], p = 0.002, 95% CI - 0.8 to - 0.2). The local skin adverse events were observed in five patients at EMLA cream applied hands. CONCLUSIONS: We conducted a comparative study to elucidate the efficacy of EMLA cream for venipuncture-pain comparing with lidocaine tape in the same patients. Our results strongly suggest that EMLA cream is more effective for venipuncture pain relief than lidocaine tape. TRIAL REGISTRATIONS: UMIN Clinical Trials Registry, UMIN000023030 . Registered 5 July 2016.