OBJECTIVE Incisional cerebrospinal fluid (CSF) leak remains a significant cause of morbidity, particularly after posterior fossa surgery, with ranges between 4 and 17% in most series. We aimed to determine whether the use of a new polyethylene glycol (PEG) dural sealant product (DuraSeal; Confluent Surgical, Waltham, MA) is effective at preventing incisional CSF leak after posterior fossa surgery. METHODS One hundred cases of posterior fossa surgery with the PEG dural sealant applied at the time of dural closure were prospectively observed from May 2005 to April 2006. All patients underwent posterior fossa craniotomy or craniectomy. Clinical histories were followed to document cases of incisional CSF leak, pseudomeningocele, meningitis, wound infection, and interventions required to treat a CSF leak or pseudomeningocele. A retrospective cohort of 100 patients treated in a similar fashion but with fibrin glue augmented dural closure served as controls. RESULTS In the PEG group, two of 100 (2%) patients developed an incisional CSF leak postoperatively. By comparison, 10 of 100 (10%) patients in whom fibrin glue was used developed an incisional CSF leak. This difference was statistically significant, with a P value of 0.03. There were no significant differences in the rates of pseudomeningocele, meningitis, or other postoperative interventions. CONCLUSION The application of PEG dural sealant to the closed dural edges may be effective at reducing incisional CSF leak after posterior fossa surgery.