The purpose of this study was to evaluate the effectiveness and safety of endoscopically guided chitosan packing in controlling intractable epistaxis. A prospective case series was performed. This is a prospective clinical study conducted in a tertiary rhinology fellowship training hospital between January 2009 and November 2009. The study population consisted of patients with intractable epistaxis that failed to respond to traditional anterior-posterior nasal packing using either a 10-cm Pope PVA Merocel or a Rapid-Rhino. The bleeding site was identified using a nasal endoscope and controlled using a pack made of a ChitoFlex chitosan dressing wrapped around a polyvinyl acetal nasal sponge. The intent-to-treat population consisted of 20 severe epistaxis subjects (8 men and 12 women) who continued to bleed despite traditional anterior-posterior nasal packing. The mean age was 67 years (±19 years). Sixteen subjects were on antiplatelets and/or anticoagulants. Eleven subjects (55%) presented with anterior epistaxis, and 7 subjects (35%) presented with posterior epistaxis. Chitosan nasal packing was performed on an outpatient basis and resulted in effective and immediate hemostasis in 19/20 subjects (95%). One subject had persistent bleeding after the first packing attempt and was successfully repacked within 30 minutes. Time to complete cessation of bleeding was 3.6 ± 2.2 minutes in the 19 subjects; the pack was removed after 48 hours, without any evidence of rebleeding or any serious side effects. Endoscopically guided chitosan packing is a safe, effective, and well-tolerated outpatient treatment for the management of intractable epistaxis.