This study aimed to investigate symptom reduction via the liposomal nasal spray LipoNasal (LN) in patients with rhinitis sicca. Tolerability and the impact on quality of life were also examined. The same parameters were established in parallel for treatment approaches with Bepanthen (BP) nasal ointment containing dexpanthenol and the Rhinomer (RH) nasal spray containing NaCl. This prospective, controlled, open-label observation study was a multicenter trial. 92 patients with rhinitis sicca were allocated to three arms according to their symptoms: LN: n = 33; BP: n = 32 and RH: n = 27. The study comprised three visits at an interval of 14 days. Efficacy was examined by the Rhinitis Sicca Symptom Score (RSSS) documented daily and at the visits based on an endoscopic evaluation. The nasal spray sensory scale was used to investigate the tolerability. Quality of life (QoL) was measured by means of the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and the "Short Form 12" of the "Impact on Health-Related Quality of Life (HRQL)" questionnaire on general quality of life. Nasal symptoms improved significantly (p = 0.001) under all three treatment approaches, reflected by the reduction in the RSSS and the Endoscopy Sum Score. A comparison of the three groups showed that no therapy was significantly superior to any of the others (p = 0.410). The tolerability of all treatments was good. Concerning the nasal moisturization, LipoNasal was evaluated better than Bepanthen and Rhinomer. Quality of life improved in all groups, but not significantly. The results show good efficacy and tolerability of the liposomal nasal spray compared to generally recognized treatments of rhinitis sicca with dexpanthenol nasal ointment and NaCl nasal spray. LipoNasal therefore constitutes a good treatment for patients suffering from dry nose.