In this metaanalysis of randomized controlled trials (RCTs) we aimed to compare the in vivo and in vitro activity and the safety of per os itraconazole and fluconazole treatment of uncomplicated acute vaginal/vulvovaginal candidiasis in nonpregnant women. We used PubMed, Scopus, Web of Science, and Cochrane Library to identify the studies that were relevant to our metaanalysis RCTs. Six RCTs were included in this study that comprised 1092 enrolled patients with signs and symptoms of vaginal/vulvovaginal candidiasis that was confirmed by microscopy and/or microbiologic cultures that were obtained from the ectocervix and/or vaginal fundus. Overall, there was no difference between itraconazole and fluconazole regarding clinical cure and improvement at the first and second scheduled visit assessments (pooled odds ratio [OR], 0.94 [95% CI, 0.6-1.48] and 1.09 [95% CI, 0.68-1.75], respectively), mycologic cure at the first and second scheduled visit assessments (OR, 0.73 [95% CI, 0.31-1.7] and 0.71 [95% CI, 0.49-1.03], respectively), withdrawal of patients because of severe adverse events (OR, 0.72 [95% CI, 0.16-3.32]), and adverse events noted from the nervous and digestive systems (OR, 1.07 [95% CI, 0.42-2.73] and 1.84 [95% CI, 0.3-11.27], respectively). In conclusion, effectiveness and safety of oral itraconazole and fluconazole in the treatment of acute uncomplicated vaginal/vulvovaginal candidiasis are similar.