In the present clinical trial the efficacy of a new nasal cream containing hyaluronic acid (Rhinogen) on mucosal wound healing has been evaluated in comparison to an ointment (H.E.C.), which is commonly prescribed for this disorder in Switzerland. A total of 56 patients recovering from surgical operation of the nasal cavities participated in this study. In both treatment groups (Rhinogen n = 27 patients, H.E.C. n = 29 patients) respiration and the condition of the nasal mucosa clearly improved. The statistical comparison between the two treatments showed a significant difference in favor of Rhinogen. With regard to the improvement in respiration, the Rhinogen-treated group showed a faster and greater progress than did the H.E.C.-treated group. Furthermore, hyaluronic acid prevented extensive crust formation during the first week of wound healing. The analysis of the efficacy of the treatments, judged by both the patients and the investigator, showed the overall superiority of Rhinogen (patients: p = 0.0041, investigator: p = 0.0023) after 6 weeks of treatment. Furthermore, Rhinogen scored significantly better than H.E.C. with respect to the organoleptic parameters of smell and sensation of cooling. Both treatments were well tolerated. No adverse reactions were reported or observed for Rhinogen, whereas three patients in the H.E.C.-treated group complained of sore throat and burning sensation when the ointment flowed down into the pharynx. In conclusion, this study confirms the therapeutic benefit of hyaluronic acid in mucosal wound healing.