Background: Radioiodine ((131) I) is effective treatment for hyperthyroidism in cats, but optimal dose to restore euthyroidism without inducing hypothyroidism is unclear. Treatment-induced hypothyroidism can lead to azotemia and reduced duration of survival. Objective: To compare efficacy and short-term outcomes of low-dose (131) I versus higher, standard-dose (131) I as treatment for hyperthyroidism. Animals: A total of 189 client-owned cats undergoing (131) I treatment for mild-to-moderate hyperthyroidism (serum T-4 >= 4.0 mu g/dL and < 13.0 mu g/dL). Methods: Prospective, nonrandomized, cohort study comparing treatment with either low-dose (2 mCi, n = 150) or standard-dose (4 mCi, n = 39) (131) I. Serum T-4, thyroid-stimulating hormone (TSH), and creatinine concentrations were measured after 1, 3, and 6 months to determine persistent hyperthyroidism, overt hypothyroidism (low T-4, high TSH), subclinical hypothyroidism (normal T-4, high TSH), and azotemia. Results: There was no significant difference in prevalence of cats with persistent hyperthyroidism between standard-and low-dose treatment groups at 3 (0% versus 5.3%; P = .34) and 6 (0% versus 3.3%; P = .51) months. Overt (18% versus 1%; P - .0005) or subclinical (46% versus 21%; P - .004) hypothyroidism was more common in cats at 6 months after standarddose (131) I. No difference in incidence of azotemia existed between groups, but cats treated with standard-dose (131) I had higher creatinine concentrations (P < .05) and higher percent rises in creatinine (P95% with reduced frequency of iatrogenic hypothyroidism and azotemia.