Object This study was conducted to compare the quality of life (QOL) in patients with neurogenic intermittent claudication (NIC) secondary to lumbar spinal stenosis (LSS). Using the 36-Item Short Form (SF-36) questionnaire, the authors compared the results obtained in patients treated with the X STOP Interspinous Process Decompression (IPD) System with those obtained in patients who underwent nonoperative therapies. Methods Patients with LSS were enrolled in a prospective 2-year multicenter study and randomized either to the X STOP or nonoperative group. The SF-36 survey was used to assess the QOL before treatment and at 6 weeks, 6 months, 1 year, and 2 years posttreatment. An analysis of variance was used to compare individual pre- and posttreatment mean SF-36 domain scores between the two groups and within each treatment group. At all posttreatment time points, the authors observed the following: 1) mean domain scores in X STOP–treated patients were significantly greater than those in patients treated nonoperatively, with the exception of the mean General Health (GH), Role Emotional, and Mental Component Summary scores at 2 years; and 2) mean posttreatment domain scores documented in X STOP–treated patients were significantly greater than mean pretreatment scores, with the exception of mean GH scores at 6, 12, and 24 months. Conclusions The results of this study demonstrate that the X STOP device is significantly more effective than non-operative therapy in improving the QOL in patients with LSS. The results are comparable with those reported in other studies involving traditional decompressive techniques for LSS and suggest that the X STOP implant can provide an effective treatment compared with nonoperative and conventional surgical therapies.