Introduction Oral isotretinoin is commonly prescribed for acne vulgaris. Several case reports and observational studies have reported serious musculoskeletal side effects; however, the incidence, imaging findings, and longitudinal follow-up data are limited for patients who develop inflammatory back pain (IBP). Objective To assess the incidence of isotretinoin-triggered axial spondyloarthropathy (SpA) in acne vulgaris patients based on clinical features and MRI findings and to examine clinical and radiological outcomes following drug withdrawal. Methods Five hundred thirteen acne patients receiving isotretinoin were screened for IBP; IBP patients were assessed for CRP, plain radiographs, andMRI of the sacroiliac joint.MRI-proven sacroiliitis was scored semi-quantitatively. Patients were followed longitudinally to assess SpA clinical course and longitudinalMRI sacroiliac joints, and CRP levels were reassessed 3 weeks after patients were symptom-free, following isotretinoin discontinuation. Results Of the 513 patients, 23.98% developed IBP. MRI-proven sacroiliitis was detected in 42.3% of the symptomatic patients or 10.1% of the cohort. Among MRI-proven sacroiliitis cases, 51.9% fulfilled the Assessment of Spondyloarthritis International Society criteria for axial SpA. Mean CRP level was 32.05 ± 17.23 mg/L at pain onset and 3.4 ± 2.7 mg/L after symptom resolution. MRI findings completely resolved within 9 months (mean 6.27 ± 1.7) after isotretinoin discontinuation. MRI scores positively correlated with baseline CRP levels and global acne grading system score, pain, and the Ankylosing Spondylitis Disease Activity Score.