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Objectives: Unilateral clear thin rhinorrhea (UCTR) can be concerning for a nasal cerebrospinal fluid (CSF) leak. Beta-2 transferrin electrophoresis has been the gold standard for initial non-invasive confirmatory testing for CSF rhinorrhea, but there can be issues with fluid collection and testing errors. Ipratropium bromide nasal spray (IBNS) is highly effective at reducing rhinitis-related rhinorrhea, and should presumably not resolve CSF rhinorrhea. This study assessed whether different clinical features and IBNS response helped predict presence or absence of CSF rhinorrhea., Methods: A prospective cohort study was conducted where all patients with UCTR had nasal fluid tested for beta-2 transferrin, and were prescribed 0.06% IBNS. Patients were diagnosed with CSF rhinorrhea or other rhinologic conditions. Clinical variables like IBNS response (rhinorrhea reduction), positional worsening, salty taste, postoperative state, female gender, and body-mass index were assessed for their ability to predict CSF rhinorrhea. Sensitivity, specificity, and predictive values and odds ratios were calculated for all clinical variables., Results: Twenty patients had CSF rhinorrhea, and 53 had non-CSF etiologies. Amongst clinical variables assessed for predicting CSF absence or presence, significant associations were shown for IBNS response (OR = 844.66, p = 0.001), positional rhinorrhea worsening (OR = 8.22, p = 0.049), and body-mass index ≥30 (OR = 2.92, p = 0.048). IBNS response demonstrated 96% sensitivity and 100% specificity, and 100% positive and 91% negative predictive values for predicting CSF rhinorrhea., Conclusions: In patients with UCTR, 0.06% IBNS response is an excellent screening tool for excluding CSF rhinorrhea, and should be considered in the diagnostic workup of CSF rhinorrhea., Level of Evidence: 2 Laryngoscope, 134:56-61, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)