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The difficult or impossible establishment of venous access is occasionally encountered in the pediatric population, especially in patients exposed to repeated surgical procedures or those with underlying comorbid features. Potential options in such situations include the intramuscular, intraosseous (IO), and intratracheal administration of medications. Although IO access is accepted as the route of choice in emergency situations, its use is not universally accepted in the operating room setting when the administration of medications is nonemergent. We report the intentional and elective use of the intra-arterial (IA) administration of vecuronium, atropine, fentanyl, and fluid during the provision of anesthesia for two infants with severe cyanotic congenital heart disease in whom venous access could not readily be obtained. The potential role of IA administration of medications is discussed and previous reports from the literature are reviewed.