Intranasal corticosteroids are considered the most effective therapy for moderate-to-severe seasonal allergic rhinitis (SAR) andrecommended first line in guidelines. It is uncertain whether intranasal antihistamines have comparable efficacy. This study was designed to compare the efficacy of azelastine (AZE; 137 micrograms/spray) and fluticasone propionate (FP; 50 micrograms/spray), bothgiven as 1 spray/nostril bid (i.e., approved dosing regimen in the United States), in SAR via a post hoc analysis of data from a previously published direct-comparison study. Six hundred ten moderate-to-severe SAR patients ( more than or equal to 12 years old) were randomized into a double-blind, placebo-controlled, parallel-group trial. The primary efficacy variable was change from baseline in reflective total nasal symptom score (rTNSS (morning and evening), over 14 days. Reflective total ocular symptom score (rTOSS) was a key secondary variable. Reflective total of seven symptom scores (rT7SS [nasal plus ocular symptoms]) and time to more than or equal to 50% reduction from baseline in these key parameters were also analyzed. AZE and FP reduced rTNSS from baseline by a similardegree (-3.25 versus -3.84; p = 0.2014). Patients experienced comparable improvement in rTOSS (-2.62 versus -2.17; p = 0.2371) and rT7SS (-5.83 versus -6.05; p = 0.7820). FP was superior to AZE in alleviating rhinorrhea (-1.15 versus -0.87;p = 0.0433), but AZE showed comparable efficacy for all other nasal and ocular symptoms. There was no clinically orstatistically significant difference between AZE (-1.17) and FP (-1.43) for reduction in the overall rhinitis quality of life questionnaire score (although FP, but not AZE, significantly differed from placebo). A similar proportion of patients in the AZEand FP groups achieved a 50% reduction in rTNSS. However, more AZE patients (53.0%) exhibited a 50% reduction inrTOSS by day 14 versus FP (39.6%), and less than or equal to 3 days faster (p = 0.028). Intranasal AZE (137 micrograms/spray) and intranasalFP (50 micrograms/spray), both 1 spray/nostril b.i.d., had comparable efficacy in symptom control in moderate-to-severe SAR.