<i>Background:</i> The ARIA (Allergic Rhinitis and its Impact on Asthma) guidelines proposed a classification for allergic rhinitis based on the duration of symptoms (intermittent or persistent) rather than on the time of allergen exposure (seasonal or perennial). There had been no placebo-controlled, randomized, clinical trial of desloratadine (DL) in patients with persistent allergic rhinitis to date. <i>Objectives:</i> To assess the efficacy and safety of DL in patients with persistent allergic rhinitis based on the ARIA classification. <i>Methods:</i> Patients 12 years of age and older with persistent allergic rhinitis were assessed over 85 days of treatment with DL 5 mg once daily (n = 360) or placebo (n = 356). The primary endpoint was the AM/PM reflective total 5-symptom score (T5SS) averaged over days 1–29. Secondary endpoints included AM/PM instantaneous T5SS and individual symptoms, therapeutic response, symptom severity assessed by a visual analogue scale and quality of life. <i>Results:</i> The mean reduction in AM/PM reflective T5SS was significantly greater with DL than placebo over days 1–29 (–3.76 vs. –2.87, p < 0.001) and on each individual day (p < 0.05). The mean AM instantaneous T5SS was significantly reduced with DL compared with placebo as early as day 2 (–1.90 vs. –1.46; p < 0.001). The therapeutic response and improvement in quality of life were significantly greater with DL than placebo (p < 0.001 for each). The frequency of treatment-related adverse events was low and similar between DL (10.0%) and placebo (8.4%). <i>Conclusions:</i> This study showed DL to be effective and safe in the treatment of persistent allergic rhinitis.