STUDY DESIGN: A retrospective review. OBJECTIVE: The purpose of this study is to determine the differential improvement of the various individual items of the Oswestry Disability Index (ODI) and to determine their relationship to other measures of Health Related Quality of Life (HRQOL). SUMMARY OF BACKGROUND DATA: The ODI is an easily scored, common, 10-item questionnaire about symptoms relevant to lumbar spine pathology. It is not clear if all of the items can be reliably applied to spine surgery. The purpose of this study is to determine the differential improvement of the various individual items of the ODI and to determine their relationship to other measures of HRQOL. METHODS: Analysis of a prospective registry of patients treated at an academic medical center was undertaken. At baseline, standardized outcome measures including ODI and SF12 PCS were collected on all patients undergoing elective fusion surgery for degenerative spondylolisthesis. Multiple linear regressions were performed using change in SF12 PCS as the dependent variable and change in ODI components as the independent variables. RESULTS: Baseline and 1-year follow-up data were collected on 196 patients (mean age 60.4 years). There were statistically significant differences in improvement among ODI items. Surprisingly, the most improvement after surgery was noted in the standing, sex life, and social life domains. The least improvement was noted in the personal care, sleeping, and sitting domains. Linear regression for change in ODI components versus change in SF-12 PCS revealed a significant correlation (R = 0.353, P ≤ 0.001). The only retained domains in the final model were change in lifting, standing, and traveling as predictors for ΔPCS. CONCLUSION: All domains of the ODI do not improve equally after surgery for degenerative spondylolisthesis. Some of the domains that improve most (e.g., sex life) have no discernible relationship to the known pathophysiology of degenerative spondylolisthesis. Based upon these results, we conclude that the item bank and composite scoring of the ODI are inappropriate for evaluating quality of life in studies of surgically treated degenerative spondylolisthesis patients. LEVEL OF EVIDENCE: 3.