The objective of this retrospective study was to evaluate hyperthyroid cats for pretreatment factors that would predict response to radioiodine therapy. Hyperthyroidism was diagnosed in 193 cats based on elevated serum thyroxine levels and/or elevated thyroid to salivary gland ratios on thyroid scintigraphy. All cats were treated with an intravenous bolus of 4 mCi of radioiodine and follow-up serum thyroxine levels were evaluated at 1 week and 1, 3, 6, and 12 months post-therapy. There was a significant relationship between pretreatment thyroxine values and post-treatment thyroxine values at all of the follow-up time points (p < 0.001). There was also a relationship between thyroid to salivary gland technetium scan ratio results and serum thyroxine values at pretreatment and at 1 week post-treatment (p = 0.02, 0.005, respectively). A greater scan ratio was associated with higher thyroxine levels at these time points, but not at 1,3, 6 or 12 months post-therapy. Ninety-eight cats pretreated with methimazole were analyzed for the effect of this drug on response to therapy. Methimazole was discontinued ≥5 days before radioiodine therapy in 58 cats and <5 days in 31 cats, in 9 cats the number of days off methimazole was unknown. There was no difference in response to radioiodine based upon when methimazole was discontinued (p = 0.70).