The efficacy of a single-dose application of miconazole varnish in the treatment of denture stomatitis was compared with miconazole gel applied three times/day for 15 days. Among 288 wearers of complete dentures 50 patients severely affected by denture stomatitis and heavily colonized by Candida, were selected. The patients were assigned randomly to two groups: a miconazole varnish group and a gel group. All patients were examined 7 times: before starting the treatment (day 0); during treatment (day 3, 7 and 14); after treatment (day 21, 28 and 35). At each examination a photograph of the palatal mucosa was obtained and quantitative cultures of Candida from the lesions and the fitting denture surface were performed. At day 14 the inflammation was reduced to the same degree in the two groups of patients. A comparison of the antifungal effect, i.e. reduction of the yeast score, showed no significant difference between the two groups. Maximum reduction of the number of yeasts was obtained at day 14. From that moment, recolonization started; thus, about 60% of the treated patients whether it was with the gel or the varnish was positive of Candida by day 35. In conclusion, the present study showed no difference in the clinical and antifungal effect of a single-dose application of miconazole varnish compared with miconazole gel. The varnish seemed to be better with respect to the posology as the total dose of miconazole is minimal and only one application is necessary. Treatment with the miconazole varnish seems particularly indicated in debilitated and non-cooperative patients suffering from Candida-associated denture stomatitis.