Objectives: To analyze the feasibility of DWI-MRI and ADC to evaluate treatment response in patients with multiple myeloma (MM). To correlate the variations of ADC and SUVmax in F-18-FDG PET-CT. Methods: 27 patients with MM that had a whole-body MRI and F-18-FDG PET-CT performed at baseline and after treatment were retrospectively recruited between February 2018 and May 2020. Three target bone lesions were selected for each patient and their ADC, SUVmax and Deauville score were measured in every study. Correlation between ADC and SUVmax of the lesions was evaluated, as well as changes in mean ADC, SUVmax, and Deauville score between studies. Patients were classified as responder or non-responder according to the IMWG, MRI (MY-RADS) and PET-CT (IMPeTUs) response criteria. Agreement between the MRI and PET-CT criteria with the IMWG criteria was evaluated. Results: The correlation between the ADC and SUVmax of all the target lesions was strong, negative and significant (r=-0.603; p < 0.001). After treatment, mean ADC in lesions from responders was significantly higher than in non-responders (1585.51 x 10(-6) mm(2)/s vs 698.17 x 10(-6) mm(2)/s; p < 0.001). SUVmax of the same lesions was significantly lower in responders than in non-responders (2.05 vs 5.33; p < 0.001). There was a very strong or strong agreement of the IMWG response criteria with both MRI (kappa = 0.852; p < 0.001) and PET (kappa = 0.767; p < 0.001) criteria. Conclusion: DWI-MRI and ADC may be used to assess treatment response in MM patients, showing a good correlation with F-18-FDG PET-CT and the IMWG response criteria.