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Study Design: Retrospective Review., Objective: To assess the impact of preoperative pain and disability on patient-reported outcome measures (PROMs) following minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) for degenerative spondylolisthesis., Summary of Background Data: Varying preoperative symptom severity in lumbar fusion patients alters perceptions of surgical success., Methods: Degenerative spondylolisthesis patients undergoing elective, primary, single-level MI-TLIF were stratified by preoperative symptom severity: Mild (VAS-B<7/ODI<50), Moderate (VAS-B≥7/ODI<50 or VAS-B<7/ODI≥50), and Severe (VAS-B≥7/ODI≥50). PROMs, Patient-reported Outcomes Measurement Information System-Physical Function (PROMIS-PF), ODI, VAS-B, VAS-Leg (VAS-L), and 9-item Patient Health Questionnaire (PHQ-9) were compared at baseline, 6 weeks, and final follow-up (μ=16.3±8.8 mo). Postoperative PROMs, magnitudes of improvement, and minimal clinically important difference (MCID) achievement rates were compared between cohorts through multivariable regression., Results: A total of 177 patients were included. Acute postoperative pain and narcotic consumption were highest in the severe cohort (P≤0.003). All preoperative PROMs worsened from mild to severe cohorts (P<0.001). All PROMs continued to be significantly different between cohorts at 6 weeks and final follow-up, with the worst scores in the Severe cohort (P≤0.003). At 6 weeks, all cohorts improved in ODI, VAS-B, VAS-L, and PHQ-9 (P≤0.003), with the Moderate cohort also improving in PROMIS-PF (P=0.017). All Cohorts improved across PROMs at the final follow-up (P≤0.044). Magnitudes of improvement in ODI, VAS-B, and PHQ-9 increased with worsening preoperative symptom severity (P≤0.042). The Moderate and Severe cohorts demonstrated higher MCID achievement in ODI, VAS-B, and PHQ-9 rates than the Mild cohort., Conclusions: Despite preoperative pain and disability severity, patients undergoing MI-TLIF for degenerative spondylolisthesis report significant improvement in physical function, pain, disability, and mental health postoperatively. Patients with increasing symptom severity continued to report worse severity postoperatively compared with those with milder symptoms preoperatively but were more likely to report larger improvements and achieve clinically meaningful improvement in disability, pain, and mental health., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)