A prospective, randomized, controlled trial was conducted to compare clinical outcomes in patients treated with an investigational interspinous spacer (Superion) versus those treated with an FDA-approved spacer (X-STOP). One hundred sixty-six patients with moderate lumbar spinal stenosis (LSS) unresponsive to conservative care were treated randomly with the Superion (n = 80) or X-STOP (n = 86) interspinous spacer. Study subjects were followed through 6 months posttreatment. Zurich Claudication Questionnaire (ZCQ) symptom severity scores improved 30% with Superion and 25% with X-STOP (both P < 0.001). Similar changes were noted in ZCQ physical function with improvements of 32% with Superion and 27% with X-STOP (both P < 0.001). Mean ZCQ patient satisfaction score ranged from 1.7 to 2.0 in both groups at all follow-up visits. The proportion of subjects that achieved at least two of three ZCQ clinical success criteria at 6 months was 75% with Superion and 67% with X-STOP. Axial pain decreased from 55 ± 27 mm at pretreatment to 22 ± 26 mm at 6 months in the Superion group (P < 0.001) and from 54 ± 29 mm to 32 ± 31 mm with X-STOP (P < 0.001). Extremity pain decreased from 61 ± 26 mm at pretreatment to 18 ± 27 mm at 6 months in the Superion group (P < 0.001) and from 64 ± 26 mm to 22 ± 30 mm with X-STOP (P < 0.001). Back function improved from 38 ± 13% to 21 ± 19% with Superion (P < 0.001) and from 40 ± 13% to 25 ± 16% with X-STOP (P < 0.001). Preliminary results suggest that the Superion interspinous spacer and the X-STOP each effectively alleviate pain and improve back function in patients with moderate LSS who are unresponsive to conservative care.