BACKGROUNDThe value of conventional magnetic resonance imaging in the differential diagnosis of thyroid nodules is limited; however, the value of multi-parameter diffusion-weighted imaging (DWI) in the quantitative evaluation of thyroid nodules has not been well determined. AIMTo determine the utility of multi-parametric DWI including mono-exponential, bi-exponential, stretched exponential, and kurtosis models for the differentiation of thyroid lesions.METHODSSeventy-nine patients (62 with benign and 17 with malignant nodules) underwent multi-b value diffusion-weighted imaging of the thyroid. Multiple DWI parameters were obtained for statistical analysis.RESULTSGood agreement was found for diffusion parameters of thyroid nodules. Malignant lesions displayed lower diffusion parameters including apparent diffusion coefficient (ADC), the true diffusion coefficient (D), the perfusion fraction (f), the distributed diffusion coefficient (DDC), the intravoxel water diffusion heterogeneity (α) and kurtosis model-derived ADC (Dapp), and higher apparent diffusional kurtosis (Kapp) than benign entities (all P < 0.01), except for the pseudodiffusion coefficient (D*) (P > 0.05). The area under the ROC curve (AUC) of the ADC(0 and 1000) was not significantly different from that of the ADC(0 and 2000), ADC(0 to 2000), ADC(0 to 1000), D, DDC, Dapp and Kapp (all P > 0.05), but was significantly higher than the AUC of D*, f and α (all P < 0.05) for differentiating benign from malignant lesions.CONCLUSIONMultiple DWI parameters including ADC, D, f, DDC, α, Dapp and Kapp could discriminate benign and malignant thyroid nodules. The metrics including D, DDC, Dapp and Kapp provide additional information with similar diagnostic performance of ADC, combination of these metrics may contribute to differentiate benign and malignant thyroid nodules. The ADC calculated with higher b values may not lead to improved diagnostic performance.