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Background: Lidocaine with epinephrine is routinely used to achieve peripheral nerve blockade in non-appendage anatomical sites due to the vasoconstrictive properties and prolonged duration. Medical recommendations suggest avoiding epinephrine use in distal appendages (i.e. fingers, toes, nose, ears, and penis) due to occurrences of ischemia or necrosis. Currently, there is dispute whether epinephrine injected in distal appendages is responsible for cases of ischemia or necrosis. Objective: To assess occurrence of ischemia following infiltration of lidocaine with epinephrine in distal appendages. Design and Methods: A systematic literature review of online databases was performed with keywords “digital,” “digits,” “epinephrine,” “ischemia,” “lidocaine,” and “necrosis.” Of the articles found, the results were limited to include metaanalyses, systematic reviews, randomized-control trials, cohort studies, humans, and studies published within the last 10 years. Further inclusion criteria consisted of “distal, “appendage,” “ears,” “fingers,” “toes,” OR “penis.” Results: There were two textbooks and 13 scientific articles included for research. In 48 cases studying the effects of ischemia or necrosis after using epinephrine, it was found that more incidents of necrosis occurred without epinephrine. Procaine had an FDA warning issued in 1948 for acidic batches. As procaine was the preferred anesthetic prior to 1950, it was procaine, and not epinephrine, as the likely agent responsible for cases of tissue necrosis. In 63 patients undergoing a Mohs procedure for digital tumors, none experienced ischemia prior to infiltration of the tumor site with 0.5% lidocaine with 1:200,000 epinephrine. Another literature review evaluated 39 studies (over 270,000 patients) for the safety of 1:100,000 to 1:200,000 with local anesthetics in digital nerve blocks. No cases reported digital necrosis following injection of epinephrine. Conclusion: Despite the recommendation to avoid lidocaine with epinephrine in distal appendages, an abundance of current literature SAFETY OF EPINEPHRINE iv suggests ischemia or necrosis related to epinephrine is extremely uncommon. For the rare instance that blood flow would ever be compromised following high doses of epinephrine, phentolamine as a reversal agent for ischemia can be used effectively.