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The eutectic mixture of local anesthetics (EMLA), by producing dermal anesthesia through contact with intact skin, has become a major indication for the reduction of pain experienced during venipuncture (VE) and intravenous (IV) insertion.The purpose of the study was to determine the mean effect sizes and moderators of EMLA cream application in reducing VE and IV insertion pain.A meta-analysis of 20 studies was conducted to determine the magnitude of the effect of EMLA cream on VE and IV insertion pain. Effect sizes were calculated three ways: weighted, unweighted, and weighted by quality index score. Potential moderating variables of sample age, premedication, therapist control, insertion site, application duration, research design, pain scale, and funding, were investigated for their influence on EMLA’s effect.EMLA cream had a large significant effect on VE pain (d = 1.05) with a 95% confidence interval from .92 to 1.34 and a large significant effect on IV insertion pain (d = 1.04) with a 95% confidence interval from .84 to 1.46. Subject age (child versus adult), type of pain scale, number of therapists, location of insertion site, premedication, funding, or study design did not appear to act as effect modifiers.EMLA cream can significantly decrease VE and IV insertion pain in 85% of the population.