Background: Persistent infection following endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) is a frustrating entity for the patient and rhinologist alike. Mupirocin nasal washes have been proposed as an efficacious treatment in such patients. Two small studies have reported excellent short-term posttreatment outcomes; however, the long-term microbiological outcomes following treatment are not known; likewise, the rate of mupirocinresistance following treatment has not been explored. Methods: This was a retrospective chart review of 61 patients with Staphylococcus aureus (S. aureus)-positive surgically-recalcitrant CRS having undergone 0.05% mupirocin nasal rinse treatment, twice daily for 4 weeks. Specific outcomes reported included posttreatment culture results, time to first posttreatment S. aureus culture, and mupirocin-sensitivity following treatment. Results: Of 57 patients meeting minimal posttreatment follow-up criteria, 42 (73.7%) progressed to microbiological failure by subsequently cultured S. aureus. Mean time to first positive culture was 144 days. Of the 42 patients who progressed to microbiological relapse, full antibiotic sensitivity data was available for 41; of these, only 1 was found to subsequently harbor a mupirocin-resistant strain of S. aureus, thus yielding a posttreatment resistance rate of 2.4%. Conclusion: Treatment with mupirocin nasal washes in S. aureus-positive, surgically recalcitrant CRS has a high microbiological failure rate, with 73.7% of patients subsequently re-culturing S. aureus. Our current treatment regime of 0.05% nasal washes twice daily for 4 weeks is associated with a posttreatment resistance rate that is consistent with other studies of topical mupirocin use, suggesting that mupirocin washes are no more likely to induce resistance than nasal vestibule decolonization in the high-risk medical or surgical patient.