Rhinosinusitis (RS), chiefly viral in origin, is increasingly widespread, and puts heavy financial burdens on society. Treatments range from home remedies and alpha-adrenergic agonistic decongestants to antibiotics, corticosteroids, and even surgery. Much discomfort, pain, individual and societal cost, could be avoided through efficient, judicious and cost-effective treatments. In absence of a specific and effective treatment for RS, saline water nasal irrigation is considered safe and beneficial. In a simple scientific approach to find a novel remedy that would target not only the symptoms but also the causes of RS, a tannin-rich hypertonic solution for nasal spray was formulated and evaluated for efficacy against traditional saline. Tannin-rich plant extracts (procyanidins or PCDs) showing anti-bacterial, influenza virus-neutralizing activity were identified in vitro, and incorporated into a hypertonic glycerol solution. A pilot randomized, single blind trial was conducted on 113 RS patients not undergoing any other treatment: 51 patients received a 3% NaCl solution as placebo saline spray (PSS), while 62 patients received the PCD-containing, hypertonic solution. 3-4 sprays of the products were applied twice daily for 21 days (maximum) or until recovery. Rhinosinusitis symptom severity scores were recorded. Although PSS proved beneficial, the PCD-glycerol solution produced a much greater, statistically significant improvement with regard to speed and degree of symptom reduction, leading to a lesser need for antibiotherapy. Results show that the use of a non-irritant hypertonic solution containing specific tannins represents a new, efficient, safe and cost effective approach to treat RS.