BACKGROUND: It is important to differentiate Graves' disease from that of painless thyroiditis in patients with thyrotoxicosis. In this study, we evaluated the usefulness of total T3 to free T4 ratio in making a differential diagnosis between Graves' disease and painless thyroiditis. METHODS: We reviewed medical records of thyrotoxic patients, who had been diagnosed with Graves' disease or painless thyroiditis, from October 2009 to July 2011. We assessed clinical characteristics, serum levels of total T3, free T4, thyroid stimulating hormone, thyrotropin-binding inhibitory immunoglobulin, and findings of 99mTechnetium thyroid scan. We analyzed the total T3/free T4 ratios between Graves' disease and painless thyroiditis patients. RESULTS: A total of 76 untreated thyrotoxic patients "49 Graves' disease and 27 painless thyroiditis" were examined. The total T3, free T4 levels and the total T3/free T4 ratios were significantly higher in patients with Graves' disease than in those with painless thyroiditis (P < 0.001). In the total T3/free T4 ratio > 73, the possibility of Graves' disease was significantly higher than in painless thyroiditis (sensitivity, 75.5%; specificity, 70.3%). The sensitivity and specificity of the total T3/free T4 ratio in patients with free T4 < 3.6 ng/dL have been increased (sensitivity, 100%; specificity, 71.4%). CONCLUSION: The total T3/free T4 ratios was useful for making a differential diagnosis between Graves' disease and painless thyroiditis.