A eutectic mixture of local anesthetics (EMLA) in cream form has been used as a topical anesthetic to reduce the pain of procedures penetrating the skin. It is generally applied for 45 to 60 minutes before the painful procedure. The purpose of this study was to determine whether a 20-minute application of EMLA is useful in reducing the pain of routine peripheral intravenous cannulation in the emergency department (ED). A blinded, randomized, placebo-controlled, paired trial compared the pain of intravenous cannulation in both hands of study subjects: one hand was treated with 20-minute EMLA cream and the other hand was treated with 20-minute placebo cream. Forty subjects identified the more painful hand and scored pain measurements of each hand using a 10-cm visual analog scale. These data failed to demonstrate any significant benefit of EMLA compared with placebo. EMLA is not useful for intravenous cannulation when used for 20-minute application times. There may be more effective and less costly ways of reducing the pain of intravenous cannulation that patients would prefer.