BACKGROUND The widespread use of broad-spectrum antibiotics has resulted in an increase in the prevalence of methicillin-resistant Staphylococcus aureus (MRSA). Its presence in sinonasal cultures in patients with sinusitis suggests its pathogenicity. However, the efficacy and safety of treatment modalities for MRSA sinusitis remain incompletely described. METHODS A retrospective chart review of six patients treated for MRSA sinusitis with outpatient intravenous (i.v.) antibiotics was performed for patient demographics, history of antibiotic use, history of prior sinus surgery, and treatment-related complications. A quality-of-life survey and endoscopically guided cultures before and after therapy were used to measure treatment outcomes. RESULTS The cohort consisted of five women and one man with a mean age of 50.8 years. All patients had undergone multiple sinus procedures with a mean number of 2.7 procedures per patient (range, 1-6 procedures). Five patients (83.3%) experienced negative cultures after outpatient i.v. antibiotics. The single patient who had persistent cultures experienced clinical and endoscopic improvement in her symptoms. The quality-of-life scores improved in five of the six patients (83.3%) after therapy. Four patients (66.7%) experienced five adverse events including allergic reaction (four events) and neutropenia (one event), all of which resolved with a change in medication. CONCLUSIONS Outpatient i.v. antibiotics may be an effective therapy for the treatment of MRSA sinusitis. The occurrence of adverse events requires a dedicated protocol to therapy. Future studies are required to investigate long-term efficacy.