To evaluate the efficacy of a nonabsorbable, synthetic graft for the reconstruction of spontaneous middle fossa (sMF) cerebrospinal fluid (CSF) leaks. Six adult patients (age ≥16 yr) who had sMF CSF leaks surgically repaired within an 18-month period at a single university hospital using synthetic, nonbiological, nonabsorbable graft (Neuro-Patch) and a retrospective control group of five patients undergoing multilayer MF repair with autologous grafts. MF repair through a combined transmastoid/MF approach using Neuro-Patch or multilayer autologous grafts. The incidence of postoperative leak within 6 months postoperatively was the main outcome measure; we also recorded the need for lumbar drain, additional hearing loss, length of inpatient stay, body mass index, previous meningitis, preoperative increased intracranial pressure, and age. In the Neuro-Patch group, there was no postoperative CSF leak without the need for lumbar drain. We observed no additional hearing loss; patients were monitored for 2 days without any readmissions. Increased intracranial pressure (four of six), previous episodes of meningitis (two of six) or obesity (five of six) did not affect patient outcomes. Demographic and prognostic factors were the same for the control group. However, one patient needed lumbar drain postoperatively because of residual leak; lumbar drain was used in one more case (two of five cases), whereas three of five patients had to stay for longer than 2 days (5 d). Our pilot study suggests the use of Neuro-Patch via combined transmastoid/MF approach as an effective technique with minimum, if any morbidity; it could be of particular benefit for patients with larger MF dura defects. A larger number of patients are required to strengthen the evidence.