Abstract Aim Recurrent aphthous ulceration is the most commonly known oral mucosal disease. Quercetin is a useful therapeutic agent for the treatment of colitis and gastric ulcer. The objective of this study was to determine the effect of topical application of quercetin in the treatment of minor aphthous ulcers. Methods and Materials Forty male patients with no known pathology of the oral mucosa other than minor aphthous ulcers were enrolled in this study. Patients were randomly divided into two groups, each consisting of 20 patients. Group 1 (control group) patients used a benzydamine hydrochloride mouthwash three times daily. Group 2 patients placed two to three dabs of quercetin three times daily directly on their ulcers. Clinical evaluation of patients included assessment of ulcer size, pain measure, and interviews regarding the topical application of quercetin in terms of consistency, taste, local tolerability, and ease of application. Results The topical application of quercetin cream to minor mouth ulcers relieved pain and produced complete healing in seven of the Group 2 patients (35 percent) in 2–4 days, 18 patients (90 percent) in 4–7 days, and 20 patients (100 percent) in 7–10 days. When comparing the mean ulcer size after 10 days, lesions in the Group 2 patients were smaller than those in Group 1, and the size difference between the two groups was significantly different (p<0.004). Also, 90 percent of patients responded that they appreciated the ease of application when using the topical quercetin, and they did not object to its consistency or taste. Conclusion Quercetin is a safe, well-tolerated, and highly effective promising new, adjunctive treatment for healing common aphthous ulcers. Clinical Significance Although aphthous ulcers typically resolve on their own in one to two weeks, the daily topical application of quercetin may be useful in accelerating the healing process of minor aphthous ulcers. Citation Hamdy AAEM, Ibrahem MAE. Management of Aphthous Ulceration with Topical Quercetin: A Randomized Clinical Trial. J Contemp Dent Pract [Internet]. 2010 July; 11(4):009-016. Available from: http://www.thejcdp. com/journal/view/volume11-issue4-hamdy