Acute rhinosinusitis is a common inflammatory condition characterized by the inflammation of the paranasal sinuses. The use of saline irrigation in the nasal passages is a well-established and effective approach for managing both acute and chronic rhinosinusitis (CRS), allergic or nonallergic, atrophic rhinitis, facilitating postoperative care following endoscopic sinus surgery as well [4]. Various topical agents can be added to lavage solution. Among this mupirocin has notable anti-staphylococcal properties. To study and compare the efficacy of mupirocin nasal irrigation with saline nasal irrigation in reducing symptoms and duration of treatment in the case of acute rhinosinusitis. In AVMC Pondicherry a randomized double blinded trial was carried out. A total of 50 patients diagnosed with acute rhinosinusitis are selected and equally divided into two groups. One group was given mupirocin nasal irrigation solution, other group was given saline nasal irrigation solution. Patient’s symptoms were evaluated at Different visits and mean symptomatic score (MSS) was used to gather data. The mean age of participants in both Group A and Group B is approximately 41.3 (± 11.632) years and 39.8(+ 10.163) years. The percentage distribution of male and female subjects is 44.0% and 56.0% in group A and in group B 36.0% and 64.0% in this present study. There was no statistical variation found in mean major symptom score between group A and group B for day 0 (0.090), but there was a statistical variation found in mean major symptom score between group A and group B for day 5 (0.04*) and day 10 (0.02*). There was no statistical variation found in duration of antibiotics course between group A and group B was 0.05*. Both mupirocin nasal irrigation and saline nasal irrigation are effective in reducing symptoms of acute rhinosinusitis. However, mupirocin nasal irrigation appears to lead to more rapid improvement in symptom severity and but may not help reduce the duration of antibiotic therapy compared to saline nasal irrigation. © 2025 Elsevier B.V., All rights reserved.