Objectives This study evaluated whether diffusion-weighted magnetic resonance imaging (DW-MRI) can be used to diagnose secondary renal amyloidosis looking specifically at the diagnostic efficacy of two apparent diffusion coefficient (ADC) measurement methods as they were used with DW-MRI. Methods The study included 24 amyloid nephropathy (AN) patients, 20 chronic kidney disease (CKD) patients, and 20 healthy volunteers (HV). ADC values were measured using two different methods: 1) the method of the region of interest indicators (ROIs) and 2) the method of drawing whole renal parenchyma (WP). The correlation between the two methods was evaluated. Results ROIs could differentiate AN-CKD (p = 0.007). ROIs and WP could differentiate AN-HV (p<0.05). However, none of the methods could differentiate CKD-HV (p>0.05). The sensitivity and specificity of the ROIs method in differentiating AN from CKD patients for 1.8 x 10(-3) cutoff ADC values were 79% and 60% and for AN-HV patients 79% and 70%. ADC values of AN patients with GFR>60 mL/min were lower than that of HV (p<0.01). Conclusion DW-MRI is a useful and non-invasive diagnostic tool in diagnosing secondary renal amyloidosis and differentiating renal amyloidosis from other CKDs. ROIs had the highest sensitivity and specificity for assessing the involvement of renal amyloidosis. MRI diagnosis of AN may obviate a renal biopsy for diagnosis.