We aimed to examine sex representation in US-based stroke clinical trials, identify trial characteristics associated with higher female enrollment (≥50%), and explore factors influencing recruitment strategies.

Stroke remains a major cause of disability and mortality in the US, with significant sex-based disparities. Although females experience well-documented differences in stroke risk and recovery compared with males, they remain underrepresented in stroke clinical trials. 

Of 456 eligible trials, only 102 (22%) enrolled ≥50% female participants. Compared with trials with <50% female enrollment, these trials more often included both sexes (99.0% vs. 65.5%) and enrolled a greater median number of female participants (22.5 vs. 10). Female-led studies were common among trials with higher female representation (40.2% vs. 37.6%). Qualitative analysis revealed that broader inclusion criteria, hybrid recruitment strategies (e.g., combining hospital and community outreach), and targeted accommodations for stroke-related disability were associated with higher female enrollment. Common barriers included exclusionary eligibility criteria, logistical challenges (e.g., transportation, caregiver requirements), and language limitations.

Despite longstanding policy emphasis on equitable enrollment, female underrepresentation in US stroke trials persists. Inclusive design, community-engaged recruitment, and structural accommodations, including support for gender-based roles such as caregiving, are influential in promoting equitable participation. Addressing sex disparities in stroke research is essential for improving the relevance, effectiveness, and fairness of stroke interventions in clinical practice.