Treatment failure for Chiari decompression is frequently associated with scarring, intradural adhesions, and recurrent loss of hindbrain space. While autograft has been our standard for hindbrain duraplasty, we investigated whether introducing anti-adhesive synthetic GORE PRECLUDE MVP Dura Substitute (expanded polytetrafluoroethylene [ePTFE] graft) was associated with improved patient outcomes. We retrospectively reviewed records of patients undergoing first-time suboccipital decompression/duraplasty for Chiari-I malformation utilizing ePTFE graft or pericranial autograft. Magnetic resonance imaging (MRI) at last follow-up was assessed for: (1) recurrent loss of dorsal hindbrain cerebrospinal fluid (CSF) space/CSF flow(cine-MR) at duraplasty site, (2) pseudomeningocele, or (3) syringomyelia improvement. Symptom recurrence warranting revision surgery was compared between cohorts. Sixty-seven patients (age 11 +/- 5 years) underwent duraplasty with pericranial autograft (n = 40) or ePTFE graft (n = 27). Perioperative morbidity did not differ between cohorts. No patients receiving ePTFE graft experienced incisional CSF leak, surgical site infection, or symptomatic pseudomeningocele. At median 8 months postoperatively, all (100%) patients with ePTFE graft maintained physiological CSF flow/decompressed hindbrain CSF space on cine-MRI versus 32 (79%) patients receiving pericranial autograft (p < 0.05). Radiographic syrinx improvement occurred in 80% of patients with ePTFE graft and 52% of patients with pericranial autograft (median time to improvement: 5 vs 12 months, respectively, p < 0.05). At median 16 months postoperatively, four (10%) patients with pericranial autograft required revision decompression versus 0 (0%) patients with ePTFE graft (p = 0.090). Duraplasty utilizing ePTFE graft was associated with improved maintenance of hindbrain space, accelerated syringomyelia improvement, and a trend toward decreased treatment failure versus pericranial autograft. Future studies of long-term outcome are warranted to confirm observed effects. Synthetic ePTFE graft is a safe alternative for duraplasty in the setting of Chiari malformation.