Background: Recurrent aphthous stomatitis (RAS) is a common disorder with hitherto unsatisfactory drug therapy. Objective: Our purpose was to evaluate the prophylactic effect of colchicine in the treatment of RAS. Methods: An open, prospective, 4-month study was conducted in 20 patients with RAS who served as their own controls. During the first 2 months of the study no medications were given and in the last 2 months colchicine, 1.5 mg/day, was prescribed. Results: The mean number of aphthae per week and the subjective daily pain scores were reduced by 71% and 77%, respectively, during colchicine treatment as compared with the previous period (p < 0.001 for both). No serious side effects of colchicine were noted. Conclusion: These findings suggest a role for continuous colchicine therapy in the prevention of RAS.