Abstract Objective To determine the diagnostic accuracy of Diffusion-Weighted Imaging (DWI) and Apparent Diffusion Coefficient (ADC) in differentiating benign from malignant thyroid nodules Study Design A cross-sectional analytical study. Methodology Thirty-four patients who determined to have suspicious thyroid nodules by ultrasonography who attend endocrinology outpatient clinic at Ain-Shams university hospital, fulfilling the inclusion and exclusion criteria, were included in the study. They were evaluated on 1.5 Tesla MRI machine with T1- and T2- weighted imaging. DWI was done using b-values of 0 and 1000 s/mm2 and ADC values were calculated for the thyroid nodules. All of these patients were subjected to full history taking, general and local clinical examination, thyroid profile, TPO Abs, ultrasound, fine needle biopsy and histopathology results were correlated with ADC values. Results The benign nodules showed facilitated diffusion while malignant nodules showed restricted diffusion. T-test was used to assess the difference in mean ADC values between benign and malignant nodules. The mean ADC value of the malignant thyroid nodules (0.8±0.1 x 10-3 mm2/s) was significantly lower than that of the benign thyroid nodules (1.3±0.2 x 10-3 mm2/s) (p-value < 0.001). ADC value of 1.15 x 10-3 mm2/s was used as a cut-off, for differentiating benign from malignant thyroid nodules. The sensitivity, specificity, PPV, NPV and diagnostic accuracy of DWI and ADC values in differentiating benign from malignant thyroid nodules were 88.2%, 92.3%, 80%, 100% and, respectively. Conclusion FNAC is gold standard diagnostic modality but has limitations. However, DWI and (ADC) is a non-invasive diagnostic tool for characterization and differentiation between benign and malignant thyroid nodules. It decreases the burden of unnecessary surgeries when pre-operative FNAC and biopsy are inconclusive