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Study Design Retrospective study. Purpose To calculate the minimum clinically important difference (MCID) for total and individual domains of the Oswestry Disability Index (ODI) and assess score distribution and changes over time in surgically treated adult spinal deformity (ASD) patients. Overview of Literature Despite the common use of ODI for assessing ASD, there are no robust studies defining MCID values for this index. Methods This study included 240 consecutive ASD patients with a minimum of 2 years of follow-up. We calculated MCID values for total and individual ODI domains using all or part of the Scoliosis Research Society-22R questionnaire as anchors. Using current MCID values, we measured the acquisition rates in patients who acquired MCID at follow-up in both total and individual ODI domains. Differences in pathology, age, and locations of the upper and lower instrumented vertebrae were analyzed. Results MCID of the total ODI score was 11%, with an area under the curve of 0.737. Each domain ranged from 0 to 2, with 1 being the most common value. In the pain and standing domains, >60% of the patients acquired MCID, although acquisition rates of the personal care, lifting, sleep, and sexual activity domains were relatively low (20%–35%). Patients with MCID had more radiographic improvement in lumbar lordosis, sagittal vertical axis, and T1 pelvic angle than those without MCID (p<0.05). Conclusions To our knowledge, this is the first study to describe MCID of ODI (11%) after ASD surgery. In the pain and standing domains, most patients acquired MCID although the rates of acquisition of MCID in the personal care, lifting, sleep, and sexual activity domains were low. Spine surgeons should counsel their patients regarding the benefits and setbacks of ASD surgery.