In minor cases, contrast extravasation may cause pain, swelling, and localized erythema. However, in more severe cases, extensive tissue and skin necrosis, ulceration, and compartment syndrome may occur, often necessitating a surgical consultation. Hyaluronidase has been used successfully in the management of extravasated contrast media in several reports. In addition, recombinant human hyaluronidase is approved for use as an adjunct in subcutaneous urography for improving resorption of radiopaque agents. In this case, a 57-year-old white female admitted for a chronic obstructive pulmonary disease exacerbation with pneumonitis and hypoxic respiratory failure experienced contrast extravasation during a computed tomographic scan of her chest. Approximately 100 mL of iodinated contrast extravasated into the right antecubital fossa, infiltrating approximately the distal two-thirds of the upper arm. Five 150-U vials of recombinant human hyaluronidase were injected in 150-U aliquots in a circle around the extravasation site using a 27-gauge needle 1 hour after the extravasation occurred. In a follow-up 4 hours later, marked improvement was observed. Sixteen hours after hyaluronidase treatment, the tissue had reverted to a near-normal state with no pain, erythema, swelling, or tenderness noted. Hyaluronidase successfully treated this extravasation of a large volume of iodinated contrast and appears to be a reasonable treatment option for more extensive subcutaneous contrast media extravasations.