Context: Oral candidiasis is the most common opportunistic infection affecting the oral mucosa. Most commonly, the lesions are caused by Candida albicans and other organisms isolated are Candida glabrata, Candida krusei, Candida parapsilosis and Candida dubliniensis. As an opportunistic infection, it is seen affecting the young, old and debilitating people. This infection is seen to be enervative, exhausting and crippling; a few routinely employed antifungal agents are used in our study. Aims: We aimed to compare the clinical and mycological effectiveness of topical fluconazole and clotrimazole in the treatment of oral candidiasis. Settings and Design: A total of 40 subjects were taken and randomly divided into two groups of 20 each. Group 1 included patients treated with topical clotrimazole and Group 2 included patients treated with topical fluconazole. Subjects and Methods: Patients were graded according to severity, and swab was taken for species identification and colony count. Patients were treated with clotrimazole and fluconazole according to their group they were also assessed post treatment for clinical signs and colony count changes. Statistical Analysis Used: Data were analyzed using the statistical package SPSS 22.0 (SPSS Inc., Chicago, IL, USA), and the level of significance was set at P < 0.05. Descriptive statistics was performed to assess the mean and standard deviation of the respective groups. Results: The clinical resolution rate of 80% and 100% was noted in the clotrimazole and fluconazole groups, respectively. The mycological cure rate of 82.52% and 86.38% was noted in the clotrimazole and fluconazole groups, respectively. Statistically significant results were obtained in clinical resolution rates and no significant results were obtained when mycological cure rates were compared. Conclusions: We conclude that the clinical cure rate of fluconazole is slightly better than clotrimazole while mycological cure rate was approximately similar.