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Few studies have examined the influence of preoperative disability through the Oswestry Disability Index (ODI) on clinical outcomes in patients undergoing anterior lumbar interbody fusion (ALIF). Patients undergoing ALIF were separated into 2 groups based on ODI<41 (lower disability) versus ODI≥41% (higher disability). Patient-reported outcomes (PROs) were collected at preoperative and postoperative 6-week/12-week/6-month/1-year/2-year time points. Physical function PROs were Patient-Reported Outcomes Measurement Information System Physical Function and 12-item Short Form Physical Component Score. Mental function PROs were 12-item Short Form Mental Component Score and Patient Health Questionnaire-9. Pain PROs were visual analog scale back and visual analog scale leg. ODI was the disability PRO. A total of 148 patients were identified, with 52 patients with lower disability. Higher disability patients demonstrated significant improvement in mental function (P ≤ 0.010, all). Lower disability patients demonstrated superior postoperative PROs in physical function, mental function, back pain, and disability outcomes (P ≤ 0.034, all). Minimum clinically important difference achievement rates for lower disability patients were higher for back pain and lower for mental function and disability outcomes (P ≤ 0.041, all). Independent of preoperative disability, patients undergoing ALIF reported significant postoperative improvement in physical function, pain, and disability outcomes. Patients with lower preoperative disability continued to report superior PROs in mental function, back pain, and disability postoperatively. Minimum clinically important difference achievement rates for lower disability patients were higher for back pain and lower in mental function and disability outcomes. Patients undergoing ALIF with higher preoperative disability may experience greater clinically meaningful improvement in mental function and disability. [ABSTRACT FROM AUTHOR]