Aim: Evaluating the Effectiveness of Topical Ketoconazole 2% in Orabase versus Ketoconazole Tablet in the Treatment of Candida-Infected Denture Stomatitis. Introduction: Denture stomatitis is a common problem among denture wearers, and treatment often involves the use of antimycotic drugs such as ketoconazole tablet. However, systemic administration of ketoconazole tablet can lead to adverse effects and poor compliance, potentially resulting in treatment failure. This study aims to compare the efficacy of topical ketoconazole 2% in orabase with ketoconazole tablet for treating denture stomatitis. Methods and Materials: Sixty patients with denture stomatitis (confirmed by positive culture) were divided into two groups. The first group received oral ketoconazole tablet (200 mg per day) for 14 days, while the second group applied topical ketoconazole 2% in orabase twice daily on the mucosal surface of the denture. Candida cultures were obtained from the palatal mucosa before treatment and on days 7 and 14 of therapy. The average colony counts were calculated for each time point. Data analysis was performed using one-way ANOVA and paired t-test (p=0.05). Results: The mean colony counts before treatment were 500 and 510 in the tablet and topical application groups, respectively. After treatment, the mean colony counts on the seventh day were 120 and 180 for the tablet and topical application groups, and on the 14th day, they were 130 and 90, respectively. There was no significant difference in colony counts between the two groups after treatment. Conclusion: Topical ketoconazole 2% in orabase can be an effective treatment option for managing denture stomatitis. This topical medication offers the advantage of fewer side effects compared to systemic administration of ketoconazole tablet, which is associated with potential complications.