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Purpose: Although several publications reported the benefits of nasal irrigation in the management of chronic rhinosinusitis and in sinonasal postoperative care, the available data are poorly controlled. The aim of this prospective randomized study was to compare the effects of sulfurous-arsenical-ferruginous thermal water nasal irrigation vs isotonic sodium chloride solution nasal irrigation after functional endoscopic sinus surgery (FESS) for chronic sinonasal disease considering the histomorphological characteristics of mucosal repair after sinus surgery. Materials and Methods: Eighty patients who consecutively underwent FESS were randomly assigned (1:1) to postoperative nasal irrigation with sulfurous-arsenical-ferruginous thermal water or isotonic sodium chloride solution for 6 months. Intraoperative and postoperative (1, 3, and 6 months) mean counts of lymphocytes, neutrophils, eosinophils, plasma cells, histiocytes, and mast cells in ethmoid biopsies were blindly determined by a pathologist. Results: Fifty-six patients underwent at least 2 postoperative biopsies. A statistically significant reduction of eosinophil count was disclosed 6 months postoperatively only after sulfurous-arsenical-ferruginous solution nasal irrigation (P = .04). After isotonic sodium chloride solution nasal irrigation, the mean eosinophil count in 6-month postoperative biopsies did not decrease. After both irrigation modalities, the mean mast cell counts in 6-month postoperative biopsies were significantly lower than in intraoperative biopsies (P < .05). Neutrophils, lymphocytes, histiocytes, and plasma cell counts were not significantly different between intraoperative vs 6-month postoperative biopsies independently from irrigation modality. Conclusions: Considering the important role of eosinophils in allergic response, we should suggest sulfurous-arsenical-ferruginous solution nasal irrigation in particular, which significantly reduces local eosinophil count, for allergic patients after FESS for chronic rhinosinusitis. [ABSTRACT FROM AUTHOR]