PURPOSE: The aim of the study was to analyze factors affecting sexual activity in individuals with and without stroke, ages 40-59 years, in a national, cross-sectional, population-based sample derived from the National Health and Nutrition Examination Survey (NHANES). DESIGN: Descriptive, cross-sectional survey. METHODS: Data were obtained from the NHANES (2011-2012) data set from individuals (N = 3,649) completing items related to cardiovascular risk factors, drugs, and sexual activity. Data were analyzed using chi-square, t tests, and logistic regression. FINDINGS: Overall, number of drugs, smoking, and depression significantly predicted sexual activity. When comparing sexually active to not sexually active, those with stroke had significantly less sexual activity (t = 2.822, p = .005) and reduced sexual activity per week or month (χ = 16.275, p = .005, df = 4). Those taking angiotensin-converting enzyme inhibitors and statins had reduced sexual activity. CONCLUSIONS/CLINICAL RELEVANCE: Findings illustrate the importance of risk factor modification and nurses engaging in sexual assessment, education, and counseling to support sexual quality of life in younger individuals with stroke.