Determine the toxicity and efficacy of a novel antiprotease topical irrigation, polyhydrated ionogen (PHI) ± MgBr2, in improving sinonasal remucosalization following surgery. Blinded, randomized controlled study. Setting. Academic. Ciliary beat frequency (CBF) of murine nasal septal explants was continuously recorded before and after addition of PHI solution to asses for ciliotoxicity. To evaluate for efficacy in remucosalization, 9 New Zealand white rabbits underwent bilateral medial-wall maxillary mucosal stripping followed by placement of an indwelling irrigation catheter. In a randomized fashion one side received 3 mL of normal saline (NS) daily, whereas the contralateral side received PHI ± MgBr2. Following a 14-day therapeutic trial, remucosalization was assessed by hematoxylin and eosin staining and immunohistochemistry for β-tubulin, a marker of cilia. A semiquantitative grading of ciliated remucosalization was applied with a chi-square test to compare the saline with the PHI ± MgBr2 treatment. Safety evaluation of the PHI solutions demonstrated no evidence of ciliotoxicity. Histologic semiquantitative analysis of maxillary sinus remucosalization demonstrated significantly more ciliated epithelium (>60%) in the majority of PHI (n = 4) and PHI with MgBr2 (n = 5) treatment compared with the saline treatment (<30%) (n = 9). This was confirmed with immunohistochemical staining for type IV β-tubulin a marker of respiratory cilia. Success of functional endoscopic sinus surgery depends on restoration of normal mucociliary clearance. Topical PHI application has previously been demonstrated to significantly increase dermal wound healing. PHI solution is not ciliotoxic, and daily topical PHI or PHI MgBr2 irrigation enhances ciliated remucosalization compared with saline.