This study investigated the gender differences in use of traditional and complementary medicine (TCM) in Ghana. Using an interviewer-administered questionnaire, we collected data from March to June 2013 from 324 randomly sampled adults in the Ashanti Region. The prevalence of TCM use in the prior 12 months was 86%. Females constituted the majority (61%) of TCM users. Female TCM users were more likely than male users to have had only a basic education, been traders (p ˂ .0001), and had health insurance (p ˂ .05). Using multiple logistic regression, TCM use was associated with urban residence for females (odds ratio [OR] = 7.82; 95% confidence interval [CI]: 1.28-47.83) but negatively related for males (OR = 0.032; 95% CI: 0.002-0.63). Being self-employed was associated with TCM use among males (OR = 7.62; 95% CI: 1.22-47.60), while females' TCM use was associated with higher income (OR = 3.72; 95% CI: 1.21-11.48) and perceived efficacy of TCM (OR = 5.60; 95% CI: 1.78-17.64). The African sociocultural structure vests household decision-making power in men but apparently not regarding TCM use, and the factors associated with TCM use largely differed by gender. These findings provide ingredients for effective health policy planning and evaluation. Adoption and modernization of TCM should apply a gendered lens.