Background: We describe the surgical technique for use of small intestine submucosal (SIS) xenograft implant for inferior turbinate reconstruction and report our early results in a pilot case series of patients suffering from symptoms consistent with empty nose syndrome (ENS). Methods: We report an observational prospective cohort study of ENS patients undergoing inferior turbinate reconstruction using porcine SIS xenograft. Effects of the procedure on quality of life (QOL) were assessed through serial 25-item Sino-Nasal Outcome Test (SNOT-25) scores and analyzed by 1-way analysis of variance (ANOVA) between the initial visit and 1, 4, and 12 weeks after surgery. Results: Three patients with ENS underwent inferior turbinate reconstruction. No unexpected complications were noted over the 12-week follow-up course. Despite mild partial reabsorption of the SIS implant, neoturbinates were maintained in all patients. The mean preoperative score SNOT-25 was 77.6 (maximum 125). The mean postoperative scores were 65 at 1 week, 57 at 4 weeks, and 55 at 12 weeks (p < 0.01). Furthermore, for the "difficulty with nasal breathing" and "nose is too open" subdomains, statistically significant improvement was also noted at weeks 4 and 12 postoperatively (p < 0.05 and p < 0.01, respectively). Conclusion: The use of porcine SIS xenograft for inferior turbinate reconstruction appears to be safe and effective in the treatment of patients diagnosed with ENS. This study demonstrates statistically significant improvement in global QOL metrics and nasal-specific subdomains following inferior turbinate reconstruction/neoturbinate creation for ENS as evaluated through serial SNOT-25 scores. (C) 2015 ARS-AAOA, LLC.