Moderate to severe persistent allergic rhinitis (AR) poses a substantial socioeconomic burden.We aimed to establish the superiority of bencycloquidium bromide (BCQB) nasal spray and BCQB combined with mometasone furoate nasal spray (MFNS) over MFNS alone in adults with moderate to severe persistent AR.In this multicenter, randomized, controlled clinical trial (NCT05038202), adults with moderate to severe persistent AR were randomly assigned to receive BCQB, MFNS, or a combination treatment for 4-week periods. Mean changes from baseline in the daily reflective runny nose, nasal congestion, sneezing, nasal itching scores, total nasal symptom score (TNSS) and Rhinoconjunctivitis Quality of Life Questionnaire scores were recorded. We also assessed the exploratory end points and adverse events.Bencycloquidium bromide led to a significant improvement in the mean change from baseline in daily reflective runny nose during the 4-week treatment, compared with MFNS (least-squares mean difference, -0.27; 95% CI, -0.44 to -0.09; P = .004). The BCQB combined with MFNS significantly improved runny nose, nasal congestion, sneezing, TNSS, and Rhinoconjunctivitis Quality of Life Questionnaire scores compared with MFNS alone, except for nasal itching. Bencycloquidium bromide significantly decreased the percent change in eosinophilic cationic protein, eotaxin, vasoactive intestinal peptide, and IL-6 levels. Treatment-emergent adverse events were similar among the three groups.Bencycloquidium bromide was superior to MFNS in reducing daily runny nose symptoms. The combination of BCQB and MFNS was superior to MFNS alone in alleviating TNSS in patients with moderate to severe persistent AR with a predominant symptom of runny nose.Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.