Local anesthetics are among the most used drugs in clinical practice. Various types of reactions have been reported and many patients are told that they are allergic to caines or are at risk of allergic reactions. We report our experience with 386 patients using skin test and progressive subcutaneous challenge in order to select a local anesthetic that could be safely used. The patients underwent specific protocol including clinical history, prick and intradermal tests, and subcutaneous incremental challenge with a local anesthetic from the amide group which was free of preservatives and vasoconstrictors. Thirteen patients showed a positive skin test: 10 with positive prick test underwent the subsequent challenge with no reactions; the three who were also positive by the intradermal route were carefully evaluated with a different drug. Eight of the patients with negative skin tests complained of various clinical symptoms after the challenge. All the patients found the local anesthetic to be well tolerated and nobody reported reactions after the clinical use. These results show that skin tests and subcutaneous challenge are safe and sufficient to reliably identify a local anesthetic that patients with a prior history of adverse reaction or at higher risk could tolerate.