Endovascular thrombectomy for medium-vessel occlusion (MeVO) stroke has emerged as a major area of clinical and research uncertainty. Unlike large-vessel occlusions, MeVO stroke encompasses substantial heterogeneity in neurological severity, occlusion location, and vessel caliber, complicating both bedside decision-making and trial design. Recent randomized trials of endovascular thrombectomy for MeVO stroke have produced heterogeneous and sometimes conflicting results, leaving clinicians uncertain about patient selection and equipoise. In this review, we examine how differences in occlusion location, vessel size, and baseline National Institutes of Health Stroke Scale across recent MeVO trials may influence observed treatment effects, safety signals, and interpretation of trial results. We review how procedural risk varies across anatomic and clinical phenotypes and summarize subgroup findings that highlight important limitations of treating MeVO stroke as a uniform entity. We then propose a pragmatic, anatomy- and severity-informed framework to guide clinical decision-making and trial design, delineating scenarios where endovascular thrombectomy is beneficial, those where harm likely outweighs benefit, and a broad intermediate group requiring individualized approaches. Lastly, we discuss implications for future trials, including the need for explicit stratification, reconsideration of outcome measures, and exploration of alternative reperfusion strategies in select MeVO populations.
Goyal et al. (2026) studied this question.