DWI using single-shot echo-planar imaging (ss-EPI) is prone to artifacts, signal-intensity dropout, and T2* blurring. Readout-segmented echo-planar imaging (rs-EPI) may improve image quality in DWI of the sacroiliac joints. The purposes of this study were, first, to qualitatively and quantitatively compare image quality between ss-EPI and rs-EPI DWI of the sacroiliac joints; and, second, to evaluate whether ADC values derived from ss-EPI and rs-EPI can differentiate disease activity in patients with axial spondyloarthritis (axSpA). This retrospective study included 75 patients who underwent ss-EPI and rs-EPI DWI of the sacroiliac joints. Patients were classified into axSpA ( = 50) and no-ax-SpA ( = 25) groups on the basis of Assessment of SpondyloArthritis International Society (ASAS) criteria. Patients in the axSpA group were assigned to one of four disease activity states using the Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP). Two radiologists independently assessed qualitative (overall image quality and diagnostic confidence) and quantitative (ADC, signal-to-noise ratio [SNR], and contrast-to-noise ratio [CNR]) imaging parameters. Readout-segmented EPI provided significantly better overall image quality, diagnostic confidence, SNR, and CNR than ss-EPI (both readers, < .001). In patients with axSpA, the correlation coefficients () of ADC values and ASDAS-CRP values were 0.456 and 0.458 for ss-EPI and 0.537 and 0.558 for rs-EPI. ADCs showed progressive increases with increasing activity state for both sequences, although these increases were more substantial for rs-EPI than for ss-EPI. Across readers, median ADCs for ss-EPI were 0.243 and 0.234 × 10 mm/s for inactive disease, 0.411 and 0.412 × 10 mm/s for moderate disease activity, 0.499 and 0.447 × 10 mm/s for high activity, and 0.671 and 0.575 × 10 mm/s for very high activity (reader 1, = .011; reader 2, = .010). Across readers, ADCs for rs-EPI were 0.236 and 0.236 × 10 mm/s for inactive disease, 0.483 and 0.477 × 10 mm/s for moderate disease activity, 0.727 and 0.692 × 10 mm/s for high activity, and 0.902 and 0.803 × 10 mm/s for very high activity (reader 1, = .002; reader 2, = .001). ADC values for ss-EPI were significantly different only between the inactive and very high disease activity groups ( < .0083, Bonferroni-corrected threshold). ADC values for rs-EPI were significantly different between the inactive and high, inactive and very high, as well as the moderate and very high disease activity groups ( < .0083, Bonferroni-corrected threshold). Readout-segmented EPI significantly improves the image quality of DWI in imaging the sacroiliac joints. In patients with axSpA, activity states are better differentiated by rs-EPI than by ss-EPI. Readout-segmented EPI is a more robust tool than ss-EPI for imaging of axSpA and should be included in routine clinical protocols for MRI of the sacroiliac joints.