To compare the safety and efficacy of fluconazole 150 mg single dose and intra-vaginal clotrimazole 200mg per day for six days in the treatment of the acute episode of vulvovaginal candidiasis (VVC). In a prospective study, 142 patients with acute clinical and mycological confirmed VVC were enrolled and divided randomly in two groups. 70 patients received intra-vaginal tablet (200mg) daily for seven days, whereas 72 patients received single dose oral fluconazole (150 mg). Second and third visits were done for all patients seven days and one month after treatment and the clinical and mycological outcomes evaluated. The analysis performed using SPSS statistical software (version 15). At the second visit, 61 patients (84.7%) were cured clinically (inflammation and discharge) and 58 patients (80.5%) mycologically in fluconazole group and 60 patients (83.3%) were cured clinically and 49 patients (70%) mycologically in clotrimazole group (P=0.01). At the third visit, only one patient in fluconazole group and 17 patients in clotrimazole group had clinical sign of VVC (P=0.001). Oral fluconazole single dose seems to be a valid and promising therapy to cure acute signs and symptoms of VVC.