Background: Validated health-related quality-of-life measures have become important standards in the evaluation of the outcomes of lumbar spine surgery. However, there are few well-defined criteria for clinical success based on these measures. The minimum clinically important difference is an important demarcation, but it could be considered a floor value rather than a goal in defining clinical success. Therefore, we sought to define thresholds of substantial clinical benefit for commonly used health-related quality-of-life measures following lumbar spine arthrodesis. Methods: Prospectively collected preoperative and one-year postoperative health-related quality-of-life measures from 357 patients who were managed with lumbar spine arthrodesis for the treatment of degenerative conditions were identified. Candidate substantial clinical benefit thresholds for the Short Form-36 physical component score, Oswestry Disability Index, and back and leg pain numeric rating scales were identified with use of receiver operating characteristic curve analysis. Receiver operating characteristic curves were used to discriminate between patients who reported being "much better" or "about the same" with use of the validated Short Form-36 health transition item and between those who reported being "mostly satisfied" or "unsure" with use of a nonvalidated but more surgery-specific satisfaction-with-results survey. For each health-related quality-of-life measure, three response parameters were used: net change, percent change, and raw score at the time of the one-year follow-up. Results: Substantial clinical benefit thresholds for the Short Form-36 physical component score were a 6.2-point net improvement, a 19.4% improvement, or a final raw score of ≥35.1 points. Substantial clinical benefit thresholds for the Oswestry Disability Index were an 18.8-point net improvement, a 36.8% improvement, or a final raw score of <31.3 points. Substantial clinical benefit thresholds for the back pain and leg pain numeric rating scales were a 2.5-point net improvement or a final raw score of <3.5 points. Substantial clinical benefit thresholds for percent change were 41.4% for the back pain numeric rating scale and 38.8% for the leg pain numeric rating scale. Conclusions: We believe that thresholds of substantial clinical benefit for commonly used health-related quality-of-life measures following lumbar spine arthrodesis are important as they describe a magnitude of change that the patient recognizes as a major improvement.