Background: The current treatments of recurrent aphthous stomatitis are not very effective and are not justified for long term using due to their potential side effects. Objective: To compare the efficacy of topical sucralfate mouthwash with topical tetracycline mouthwash in recurrent aphthous stomatitis. Patients and Methods: In a randomized matched clinical trial, 60 patients with recurrent aphthous stomatitis fulfilling our inclusion criteria, referred to skin clinics affiliated to Skin Research Center in Shahid Beheshti University of Medical Sciences in 1380-81 were assessed. The patients were randomly divided in two groups, matched for age and type of the ulcer. The case group (26 patients) used a mouthwash containing 1gr sucralfate per 15cc, and the control group (34 patients) used a mouthwash containing 250mg tetracycline per 15cc, four times a day and were assessed every 2 weeks. The data were analyzed by chi-square and t-tests (P<0.05). Results: There were no significant difference between two groups regarding the frequency, healing time and pain of the aphthous lesions. Patients were more satisfied with the sucralfate suspension than tetracycline suspension in the end of treatment period (P<0.03) and in the end of follow up period (P<0.04). No side effects were seen in two group. Conclusion: Sucralfate suspension mouthwash can be considered equally effective as tetracycline mouthwash in treating recurrent aphthous stomatitis. It can be considered as a special modality for aphthous ulcer treatment due to lack of systemic toxicity and side effects even if accidentally swallowed or absorbed through mucosal surfaces.