Functional endoscopic sinus surgery is considered the standard therapeutic procedure for chronic rhinosinusitis and nasal polyposis after failure of medical treatment. We tested the hypothesis that the healing outcome after surgery was correlated to the secretion profile of gelatinase-B (matrix metalloproteinase-9 [MMP-9]) and transforming growth factor-beta1 (TGF-beta1) in nasal fluid. We performed a prospective study in 36 patients bilaterally operated for chronic rhinosinusitits or nasal polyposis and the healing quality was evaluated until 6 months after surgery by standardized nasal endoscopy, using a visual analog scale. Before functional endoscopic sinus surgery and during the postoperative period, TGF-beta1 and MMP-9 in nasal secretions were measured by enzyme-linked immunosorbent assay. Both MMP-9 and TGF-beta1 showed a significant increase initially after surgery. The healing quality after 6 months was significantly and independently correlated to preoperative MMP-9 concentrations in nasal secretions (p = 0.03), initial disease (p = 0.03), and previous sinus surgery (p = 0.004). Furthermore, concentrations of MMP-9 were significantly lower in patients with good healing (visual analog scale < 3) from week 3 to month 6 compared to patients with poor healing. MMP-9 is the first objective factor suitable to predict and monitor the healing quality after sinus surgery, indicating MMP-9 as a possible therapeutic target.