Background <p>Sacroiliitis is a major cause of inflammatory low back pain in young adults and a key feature of spondyloarthritis (SpA), but it may also occur with infection, pregnancy, or drug exposure. Isotretinoin, widely used for severe acne, can rarely induce sacroiliitis.</p> Aim <p>This study aimed to compare the MRI characteristics of isotretinoin-induced sacroiliitis with those of axial spondyloarthritis (axSpA).</p> Methods <p>The study population consisted of 68 patients, comprising 28 with isotretinoin-induced sacroiliitis (median age 24 years; 5 males) and 40 with axSpA (median age 30 years; 26 males). MRI scans were assessed for active inflammatory lesions (bone marrow edema, synovitis, capsulitis, enthesitis) and early structural lesions (erosion, fat metaplasia). SPARCC scoring was performed using the standardized 0–72 system. Ankylosis and sclerosis were not included as it was absent in both groups. Group comparisons were conducted using the Mann–Whitney U test, chi-square test, or Fisher’s exact test.</p> Results <p>While isotretinoin-induced sacroiliitis showed a purely inflammatory pattern without structural lesions, patients with axSpA exhibited both active inflammatory and structural lesions. Erosions and fat metaplasia were observed exclusively in axSpA patients (<i>p</i> &lt; 0.001). Bilateral and symmetric involvement, as well as higher SPARCC scores, were significantly more frequent in axSpA (<i>p</i> &lt; 0.05).</p> Conclusion <p>Isotretinoin-induced and axSpA sacroiliitis exhibit distinct MRI characteristics. Erosions and fat metaplasia are specific markers of axSpA, whereas isotretinoin-induced sacroiliitis represents a reversible, non-destructive inflammatory process. The present results may assist clinicians and radiologists in distinguishing between these two conditions in clinical practice.</p>