Intranasal corticosteroids are increasingly used to treat allergic rhinitis and their long-term use is generally safe. However, the long-term safety of each molecule should be assessed. The main aim of this multicenter, prospective, randomized, open-label study was to evaluate the effect of triamcinolone acetonide aqueous intranasal spray on nasal mucosal thickness, macroscopic appearance, and mucociliary function. Patients with perennial allergic rhinitis were treated with triamcinolone acetonide 220 micrograms/day for six months. Nasal biopsies taken before and after treatment were compared with biopsies from patients who had been randomized to oral cetirizine 10 mg day or intranasal beclomethasone dipropionate 400 micrograms/day. In the evaluable population (n = 70), there were no significant differences between groups in terms of histologically evaluated thickness and endoscopically evaluated macroscopic appearance of the nasal mucosa, or indigocarmine saccharine test mucociliary function. In the intent-to-treat population (n = 92), there was no difference between treatment groups in the incidence of overall adverse events. This study indicates that sustained treatment with intranasal triamcinolone acetonide does not lead to atrophy of the nasal mucosa or impairment of mucociliary function.