Objectives: Recurrent oral aphthous ulceration is a common condition treated with topical anti-inflammatory drugs, such as triamcinolone acetonide in Orabase (Kenalog in Orabase, Bristol-Myers Squibb). The aim of the study was to synthesize a novel dental paste containing dexamethasone and assess the therapeutic effect of this paste in comparison with a commonly used treatment, triamcinolone acetonide in Orabase, in oral aphthous ulceration. Method and Materials: The design was a case-control study. The setting was the laboratory of postgraduate students in the College of Pharmacy, University of Mosul, Iraq. Clinical evaluation of the paste was conducted in the outpatient clinic of the Oral Medicine Department, College of Dentistry, University of Baghdad, Iraq. The novel paste (named dexamucobase) was prepared under aseptic conditions and evaluated for its therapeutic effect in 53 patients with recurrent aphthous stomatitis, in comparison with 37 patients treated with triamcinolone acetonide in Orabase. Results: Healing of the ulcer was significantly faster (P .001), and adverse effects were significantly reduced (P .01) for the dexamucobase treatment compared to Kenalog in Orabase. There was no significant difference in the speed of pain reduction between the dexamucobase treatment compared to Kenalog in Orabase. Conclusions: The novel dexamucobase was found to be equally effective in treating oral aphthous ulceration, with some advantages, as the widely used preparation Kenalog in Orabase. Keywords: aphthous, Orabase, oral ulceration, topical formulation, triamcinolone