Radioidine I-131 treatment, consisting of a subcutaneous injection of a radioactive iodine, is considered the treatment of choice for feline hyperthyroidism. In guinea pigs, hyperthyroidism is also common. Review articles and individual case reports have suggested that radioidine I-131 should be the treatment of choice in guinea pigs with hyperthyroidism. We extracted all guinea pigs treated with, or managed after, radioidine I-131 at two veterinary teaching hospital. A total of 8 guinea pigs received 9 radioiodine I-131 injections. All guinea pigs for which the information was available were initially treated with methimazole without clinical response. Seven out of 8 guinea pigs had a palpable structure at the level of the neck, consistent with a thyroid nodule. All the injections consisted in 1 millicurie administered subcutaneously. After the injection, the guinea pigs stayed an average of 4.3 days in hospital until radioactive levels were considered acceptable for discharge. No significant side effects were noted following the injection. Of the 8 guinea pigs treated, at least 3 required further treatment (1 surgical, 1 repeated injection, 1 medical) following the initial radioidine I-131 injection. Although radioidine I-131 treatment decreased clinical signs in some guinea pigs, a significant proportion of patients required further treatment. A higher dose of I-131 or the use of different inclusion criteria may be required to reduce recurrences.