In this retrospective study, we evaluate the efficacy and safety of lithium as a second-line treatment of hyperthyroidism. The data were retrieved from the hospital recordings of 12 patients with a mean age of 42 years. All patients had Graves disease, and they had initially been treated with propylthiouracil. Indications for the change of treatment to lithium were elevation of transaminases (n = 5), agranulocytosis (n = 2), allergic reaction (n = 1), elevation of transaminases and allergy (n = 2), dyspepsia (n = 1), and resistance to propylthiouracil therapy (n = 1). A total of 900 mg lithium daily was given in 3 divided doses. One patient experienced an allergic reaction to lithium with a severe urticarial rash after the second dose. The mean follow up with lithium therapy in the remaining 11 patients was 36 days. Euthyroidism was achieved in 2 patients after 45 and 120 days of lithium treatment. In 9 patients who received lithium, the thyroid hormone levels tended to decline. Nine patients received radioactive iodine (RAI) therapy and 2 thyroid surgery as definitive treatment. The lithium therapy was generally well tolerated except in 1 patient with a high serum lithium level, nausea, and vomiting. Our results suggest that lithium has a weak antithyroid effect and can restore euthyroidism in a small number of patients. It can be tried as a second-line, symptomatic treatment when adverse reaction or resistance to thionamides occurs.