Patient-provider communication surrounding menopause symptoms and treatment is often limited. We developed and evaluated a health literacy-appropriate discussion guide to support patient education. A cross-sectional randomized study was conducted among 100 English-speaking women, aged 45-60 years, in Chicago, IL, and Durham, NC. Participants were randomly assigned to review either the discussion guide or a standard education material ( = 50 per arm) and to complete an open book knowledge questionnaire; they then rated the appearance and quality of both materials. Bivariate analyses examined knowledge and satisfaction by study arm and across sociodemographic characteristics. Multivariable models tested the effectiveness of the discussion guide to improve knowledge compared with the standard material. Women receiving the discussion guide demonstrated significantly higher knowledge scores compared with those who reviewed the standard material (mean  = 20.0, standard deviation [SD] = 2.7, vs. = 18.1, SD = 2.6; < 0.001); 82.0% of those exposed to the discussion guide correctly answered ≥85% of knowledge items compared with only 48.0% of those reviewing the standard material ( < 0.001). In multivariable analyses, participants receiving the discussion guide displayed significantly greater knowledge in comparison with those receiving the standard material regardless of whether knowledge was examined as a score ( = 1.9, 95% confidence interval [CI]: 0.9-2.9, < 0.001) or 85% threshold (odds ratio: 5.7, 95% CI: 2.0-16.2, < 0.001). More than two-thirds of women (68%) preferred the discussion guide; it was rated highly in terms of appearance and content. The discussion guide improved understanding of menopause symptoms and treatment options in comparison with a current standard and was well received by a diverse audience.