Chronic rhinosinusitis (CRS) is one of the most common chronic conditions in the United States. There is a significant subpopulation of CRS patients who remain resistant to cure despite rigorous treatment regimens including surgery, allergy therapy, and prolonged antibiotic therapy. Antimicrobial photodynamic therapy (aPDT) is a noninvasive nonantibiotic broad spectrum antimicrobial treatment. Our previous in vitro studies demonstrated that aPDT reduced CRS polymicrobial planktonic bacteria and fungi by >99.9% after a single treatment. However, prior to human treatment, the effectiveness of aPDT to eradicate polymicrobial biofilms in a maxillary sinus cavity must be demonstrated. The objective of this study was to demonstrate the effectiveness of a noninvasive aPDT treatment of antibiotic resistant biofilms known to cause CRS in a novel anatomically correct maxillary sinus in vitro model using an enhanced photosensitizer solution.