Objective: To evaluate 3 Tesla (T) whole-body diffusion-weighted magnetic resonance imaging (WB DWI) for early treatment assessment in aggressive non-Hodgkin lymphoma (NHL). Methods: Fourteen patients with NHL treated with standard chemotherapy underwent 3-T WB DWI before and 2 and 4 weeks during treatment, using b-values of 0-1000 s/mm from which the apparent diffusion coefficient (ADC) was calculated. Patient follow-up (average 20.3 months, range 15-23 months) was the reference standard. Volume and ADC changes between baseline and 2 weeks (Vratio, ADCratio) and 4 weeks (Vratio, ADCratio) of responding and non-responding lesions (lymph node and organ lesions) were compared using Mann-Whitney U tests. The per patient values of Vratio and ADCratio to predict progression-free survival were determined with a log-rank test. Results: Eight patients showed complete remission and 6 showed tumour progression. The ADCratio and ADCratio differed significantly in lesions showing tumour progression versus complete remission (ADCratio = 4 ± 21% versus 119 ± 68%; ADCratio = 18 ± 61% versus 155 ± 78%; both P < 0.0001); the Vratio and Vratio did not (P > 0.05). Per body region, the ADCratio showed a negative predictive value of 100% and positive predictive value of 86%. Per patient, the ADCratio and ADCratio correlated significantly with progression-free survival (P < 0.05). Conclusion: 3-T WB DWI with ADC quantification may enable early treatment assessment of aggressive NHL.