Introduction: Allergic rhinitis (AR) impacts around 25% of the worldwide population. However, cost, safety, and a high dissatisfaction rate with numerous conventional medications continues to be an issue in the largest patient surveys, due primarily to a lack of efficacy on nasal congestion. Our previously published randomized trial demonstrated a significant reduction in cold and flu-like symptoms, and a secondary potential observation of a decrease in nasal congestion with an oral yeast-derived compound; therefore, the objective of this study was to test the effects of this same product on nasal congestion and other notable AR symptoms., Methods: A 12-week, randomized, double-blind, placebo-controlled clinical trial of 96 healthy subjects with a recent clinically documented history of seasonal allergies and AR was conducted. Participants received once-daily supplementation with 500 mg of a dried, modified Saccharomyces cerevisiae oral fermentation product (EpiCor, Embria Health Sciences, Ankeny, Iowa, USA) or placebo during the 12-week period of the highest recorded concentrations of total pollen counts for this Midwest geographic area. Clinical outcome measurements included in-clinic examinations, validated questionnaire and standard diary, and serologic analysis at baseline, 6 and 12 weeks., Results: During the highest pollen count period (weeks 1-6), EpiCor significantly reduced the mean severity of specific AR symptoms, including a significant reduction in nasal congestion (P=0.04), rhinorrhea (P=0.005), and a nonsignificant reduction in ocular discharge symptoms. A significantly (P=0.04) reduced total number of days with nasal congestion (12.5 fewer days) favored EpiCor compared with placebo, as did the nasal congestion section of the quality of life questionnaire (P=0.04). Subjects receiving the intervention also experienced significantly (P=0.03) higher salivary IgA levels. Adverse events were similar to placebo., Conclusion: This yeast-derived product appeared to be safe and efficacious, and should receive more clinical research with and without standard medications to reduce the impact of seasonal allergies, especially AR-induced nasal congestion.