Aim. To substantiate the clinical and experimental effectiveness of the herbal medicine Sinupret® extract for acute rhinosinusitis (ARS), with an emphasis on the strategy of rational use of antibiotics. Materials and methods. A meta-analysis of clinical studies ARhiSi-1 (EudraCT No. 2008-002794-13) and ARhiSi-2 (EudraCT No. 2009-016682-28), which included 676 patients, was performed. The main focus was on reducing Symptom Severity Scale (SSS) scores and improving Sinus Osteopathy Test (SNOT-20) scores with Sinupret® extract. In addition, a retrospective cohort study involving 203,382 patients was conducted to compare the real-world effectiveness of Sinupret® extract in reducing ARS-related side effects with antibiotics and other conventional treatments. Results. The use of the drug Sinupret® extract contributed to the improvement of symptoms of ARS, which was reflected in a decrease in the average score on the CVS by 1.9 points (p0.0001) and an improvement in the quality of life (QoL) of patients according to the SNOT-2 test, by 3.5 points (p=0.001) compared to placebo. In patients with moderate and severe symptoms, the effect of Sinupret® extract was even more significant (PVS -2.3 points; p0.0001; SNOT-20 -4.9 points; p=0.0158). Moreover, the use of the drug Sinupret® extract showed equal or greater effectiveness in reducing the risk of adverse outcomes associated with ARS, such as prescription of antibiotics, prolongation of illness by ≥7 days or the need to visit a doctor, especially compared with antibiotics. Conclusion. Sinupret® extract is a safe and effective treatment for ARS, which may help reduce the overuse of antibiotics.