- The frequency of recurrent aphthous stomatitis (RAS), the most common oral mucosa lesions seen in primary care, is up to 25% in the general population. However, there has been no optimal therapeutic approach. Our objective was to confirm our previous clinical observation of the beneficial treatment of RAS with vitamin B(12). A randomized, double-blind, placebo-controlled trial was done using primary care patients. A sublingual a dose of 1000 mcg of vitamin B(12) was used in patients in the intervention group for 6 months. In total, 58 patients suffering from RAS participated in the study: 31 were included in the intervention group and 27 were included in control group. All parameters of RAS among patients in the intervention group were recorded and compared with the control group. The duration of outbreaks, the number of ulcers, and the level of pain were reduced significantly (P < .05) at 5 and 6 months of treatment with vitamin B(12), regardless of initial vitamin B(12) levels in the blood. During the last month of treatment a significant number of participants in the intervention group reached "no aphthous ulcers status" (74.1% vs 32.0%; P < .01). Vitamin B(12) treatment, which is simple, inexpensive, and low-risk, seems to be effective for patients suffering from RAS, regardless of the serum vitamin B(12) level.