Background: As the treatment approaches of Graves’ disease (GD) and thyroiditis are different, the differential diagnosis is essential. Aim: To assess the diagnostic value of free triiodothyronine (FT3) to free thyroxine (FT4) ratio for differentiation between GD and destructive thyroiditis. Subjects and Methods: The present study was conducted on 100 newly diagnosed thyrotoxicosis patients; 61 with thyroiditis (group 1) and 39 with GD (group 2) and 20 healthy, age-matched subjects representing a control group (Group 3). All participants underwent medical history taking and clinical examination, serum levels of thyroid-stimulating hormone (TSH), FT3, and FT4 were measured, Technetium 99m thyroid Scan was done to all recruited patients. Results: The present results recorded significant increases in FT3, FT4, and decreases in TSH levels in Graves’ disease group than in the thyroiditis group. There was a statistically significant difference between the study groups regarding FT3/FT4 ratio, which was lower in thyroiditis group than in Graves’ disease group (0.21± 0.03 in group 1 vs 0.35±0.18 in group 2, p-value <0.01), while there was no significant difference between thyroiditis group and the control group. The FT3/FT4 ratio showed a predictive value, with an area under the ROC curve (AUC) of 0.936 (95%CI, 0.876-0.995) for Graves' disease vs. thyroiditis (P < 0.001). Based on the cutoff value of this ratio of more than 0.269 offered a sensitivity of 89.7% and specificity of 91.8%. Conclusion: The results of the present study demonstrated that free thyroid hormones and the FT3/FT4 ratio are useful to differentiate Graves’ disease from destructive thyroiditis.