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Introduction: Multiple Myeloma (MM) represents a malignant proliferation of plasma cells derived from a single clone. Imaging of the skeleton beyond symptomatic areas is useful for myeloma staging and subsequent follow-up for treatment response and disease relapse. Despite research comparing the Dixon sequence to conventional sequences in a variety of musculoskeletal disorders, there is a lack of studies regarding the Dixon sequence's application in MM. Aim: To compare the contrast of MM focal lesions in all four T2-weighted Dixon and Conventional T1-weighted spin-echo and Short Tau Inversion Recovery (STIR) images. Materials and Methods: This cross-sectional study was conducted in the Department of Radiology at Kovai Medical Centre and Hospitals (KMCH), Coimbatore, Tamil Nadu, India. All newly diagnosed and known cases of MM, either biopsyproven or strongly suspected based on other diagnostic testing conforming to International Myeloma Working Group (IMWG) criteria from December 2020 to July 2022, were included in the study. A total of 43 patients with 142 focal MM lesions were included. Contrast between focal MM lesions and surrounding bone marrow was calculated on T1-weighted spin-echo, STIR, and T2-weighted Dixon (all four) images. Statistical analysis was done using repeated measures of Analysis of Variance (ANOVA) with Bonferroni correction to control the type I error on multiple comparisons to find the significant difference between multivariate analyses. A probability value of 0.05 was considered a significant level for all statistical tools. Results: The study population consisted of 21 men and 22 women with a mean age of 65.3±8.6 years {Mean±Standard Deviation (SD)}. Contrast values in all four T2 Dixon images, STIR, and T1-weighted images were as follows: T2 Dixon Fat-only (FO) images (0.86.±0.09) (SD); range: (0.46-0.99), T2-weighted Dixon Water-only (WO) images (0.54±0.14) (SD); range: (0.14-0.82), T2 Dixon In-phase (IP) images (0.20±0.13) (SD); range: (0.02-0.41), T2-weighted Dixon Out-phase (OP) images (0.53±0.19) (SD); range: (0.12-0.87), STIR images (0.47±0.12) (SD); range: (0.12-0.73), and T1 images (0.23±0.12) (SD); range: (0.01-0.55). The mean contrast was highest on T2 Dixon fat-only images (p<0.0005) compared to T1 images, with the lowest contrast seen in IP images and intermediate values in OP images. Conclusion: In conclusion, fat-only images of the T2 multipoint Dixon sequence provide significant contrast compared to conventional T1-weighted imaging. Dixon water-only images provide fat suppression that is not inferior to STIR images. While Dixon techniques in the diagnosis of MM did not significantly differ from the conventional sequence, Dixon stands out from conventional sequences when considering the study duration and contrast between the lesion and normal bone marrow. [ABSTRACT FROM AUTHOR]