No safe and convenient regimen has proved to be effective for the management of recurrent vulvovaginal candidiasis. After inducing clinical remission with open-label fluconazole given in three 150-mg doses at 72-hour intervals, we randomly assigned 387 women with recurrent vulvovaginal candidiasis to receive treatment with fluconazole (150 mg) or placebo weekly for six months, followed by six months of observation without therapy. The primary outcome measure was the proportion of women in clinical remission at the end of the first six-month period. Secondary efficacy measures were the clinical outcome at 12 months, vaginal mycologic status, and time to recurrence on the basis of Kaplan–Meier analysis. Weekly treatment with fluconazole was effective in preventing symptomatic vulvovaginal candidiasis. The proportions of women who remained disease-free at 6, 9, and 12 months in the fluconazole group were 90.8 percent, 73.2 percent, and 42.9 percent, as compared with 35.9 percent, 27.8 percent, and 21.9 percent, respectively, in the placebo group (P< 0.001). The median time to clinical recurrence in the fluconazole group was 10.2 months, as compared with 4.0 months in the placebo group (PCandida albicans or of superinfection with C. glabrata. Fluconazole was discontinued in one patient because of headache. Long-term weekly treatment with fluconazole can reduce the rate of recurrence of symptomatic vulvovaginal candidiasis. However, a long-term cure remains difficult to achieve.