Introduction: Vulvovaginal candidiasis (VVC) is a common cause of vaginal discharge in women of reproductive age-group.It affects 75% of women at least once during their lifetime and 10% of them have recurrent episodes.Most common offending organism is Candida albicans, and Candida glabrata being the most common non albicans species.Based on clinical presentation, microbiology, host factor like immunosuppression and recurrence, VVC is classified into complicated and uncomplicated VVC. The treatment of VVC is reasonably effective with a range of oral and intravaginal agents with Azoles being the predominant antifungals used. Aim And Objective: To compare the safety and efficacy of oral tablet fluconazole 150 mg single dose with intravaginal sertaconazole 500mg in the treatment of vulvovaginal candidiasis. MATERIALS AND METHODS: After obtaining informed consent, 100 patients who were clinically and mycologically confirmed to have vulvovaginal candidiasis were included in the study. They were randomly assigned into 2 groups, containing 50 patients each. Group A was treated with single dose of oral tablet fluconazole 150mg and group B was treated with sertaconazole 500mg vaginal pessary.The patients were reviewed at day 7 and 14 after the treatment. At each visit, symptomatic and mycological improvements were assessed and recorded. Results: A total of 97 patients completed the study.The symptomatic cure rate in both the groups at day 7 was 64.58% and 81.63% and in day 14 was 95.8% and 91.8% respectively in each group.The mycological cure rate in both groups at day 7 was 54.1%and 65.3% and day 14 was 75.1% and 85.7% respectively. Conclusion: Treatment of VVC with single dose Sertaconazole 500mg vaginal pessary results in rapid symptom clearance and lesser recurrence rate than oral Fluconazole 150mg tablet in the treatment of uncomplicated VVC, in women with personal preference of vaginal route of drug administration without significant drug interactions and adverse effects. This can also be beneficial in the era of emerging fluconazole resistance.