Genitourinary syndrome of menopause significantly affects the quality of life in postmenopausal women with few evidence-based alternatives to vaginal estrogen for women with contraindications. This systematic review evaluates the evidence for vaginal vitamin E efficacy in reducing patient-reported genitourinary symptoms in healthy postmenopausal women compared to placebo or vaginal control therapy. This systematic review evaluated randomized controlled trials before October 2020 that assessed the efficacy of vitamin E vaginal suppositories in reducing genitourinary symptoms in postmenopausal women compared with a control group of healthy postmenopausal women. Outcomes included patient-perceived genitourinary symptoms. Of the 31 studies, four met the inclusion criteria. One 8-week trial (n = 42) found a significant reduction in vaginal symptoms in the 1 mg vitamin E group than the placebo group (difference in means, 5.3; 95% confidence interval [CI], 4.4 to 6.2). Another 8-week trial (n = 40) found 5 mg vaginal hyaluronic acid superior to 1 mg vitamin E (difference in means –0.50, 95% CI, –0.95 to –0.05). Two 12-week trials (n = 52 in each) found no difference between 0.5 g vaginal estrogen and 100 IU vaginal vitamin E in healthy postmenopausal women (difference in means: –0.19, 95% CI, –4.4 to 4.0, and −3.47, 95% CI, −13.8 to 6.8). Evidence from small, limited studies suggests that vaginal vitamin E may be effective in alleviating symptoms of genitourinary syndrome of menopause; however, additional high-quality studies are needed to determine efficacy, ideal dosing, and long-term safety.