Background: Recent studies reveal deficiencies in stroke awareness and knowledge of risk factors among women. Existing stroke education interventions may not address common and sex-specific risk factors in the population with the highest stroke-related rate of mortality. Objective: This pilot study assessed the efficacy of a technology-enhanced, sex-specific educational program (“SISTERS”) for women’s knowledge of stroke. Methods: This was an experimental pretest-posttest design. The sample consisted of 150 women (mean age, 55 years) with at least 1 stroke risk factor. Participants were randomized to either the intervention (n = 75) or control (n = 75) group. Data were collected at baseline and at a 2-week posttest. Results: There was no statistically significant difference in mean knowledge score (P = .67), mean confidence score (P = .77), or mean accuracy score (P = .75) between the intervention and control groups at posttest. Regression analysis revealed that older age was associated with lower knowledge scores (P < .001) and lower confidence scores (P < .001). After controlling for age, the SISTERS program was associated with a statistically significant difference in knowledge (P < .001) and confidence (P < .001). Conclusions: Although no change occurred overall, after controlling for age, there was a statistically significant benefit. Older women may have less comfort with technology and require consideration for cognitive differences.