Background <p>Chronic rhinosinusitis (CRS) is a common inflammatory condition associated with substantial morbidity and impaired quality of life. Nasal saline irrigation is a cornerstone of medical therapy, while topical hyaluronic acid has been proposed as a potential adjunct owing to its mucosal hydrating and anti-inflammatory properties. This systematic review and meta-analysis aimed to evaluate the effectiveness of topical hyaluronic acid compared with nasal saline for the medical management of CRS.</p> Materials and methods <p>A systematic search of MEDLINE, Embase, CENTRAL, Scopus, and Web of Science was conducted from inception without date restriction. Prospective randomized and non-randomized controlled studies comparing topical hyaluronic acid with nasal saline in adult patients with CRS were included. Postoperative studies and retrospective designs were excluded. Risk of bias was assessed using RoB 2.0 and ROBINS-I tools, and certainty of evidence was graded using GRADE. Random-effects meta-analyses were performed for patient-reported nasal symptoms and endoscopic scores using standardized mean differences.</p> Results <p>Four prospective controlled studies involving 189 patients met inclusion criteria. Meta-analysis demonstrated no statistically significant difference between hyaluronic acid and nasal saline for nasal symptoms or endoscopic appearance. Substantial heterogeneity was observed across studies. Hyaluronic acid was well tolerated, with few reported adverse events. Certainty of evidence for nasal symptom outcomes was rated as very low.</p> Conclusion <p>Current low-certainty evidence does not demonstrate a clear benefit of topical hyaluronic acid over nasal saline for medical management of CRS. Routine use cannot be supported on the basis of existing evidence alone, and further high-quality trials with standardized protocols and outcomes are required to draw definitive conclusions.</p>