Abstract Background and aims The optimal prehospital referral strategy for patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO) remains controversial. This systematic review and meta-analysis compared the clinical outcomes of mothership versus drip-and-ship strategies (Fig. 1). Methods A systematic review of PubMed, Embase, Web of Science, and the Cochrane Library from inception to November 2025 identified studies comparing mothership and drip-and-ship strategies in AIS-LVO patients undergoing mechanical thrombectomy (Fig. 2). Random-effects meta-analyses were performed to estimate pooled odds ratios (ORs) for primary efficacy outcomes, including 90-day mRS 0–2, 90-day mRS 0–3, and successful recanalization. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and 90-day all-cause mortality. Results A total of 42 cohort studies comprising 25,005 patients were included. The mothership strategy was associated with a 15% increased likelihood of achieving 90-day mRS 0–2 (OR 1.15, 95%CI 1.03–1.29, I2=53%) (Fig. 3). However, no statistically significant between-group differences were observed for 90-day mRS 0–3 (OR: 1.12, 95% CI: 0.97–1.29; I2 = 52%), successful recanalization (OR: 1.03, 95% CI: 0.90–1.18; I2 = 60%), sICH (OR: 0.84, 95% CI: 0.69–1.02; I2 = 22%), and 90-day mortality (OR: 0.99, 95% CI: 0.85–1.15; I2 = 60%). Conclusions The mothership strategy was associated with better 90-day functional independence (mRS 0–2) compared with drip-and-ship, while no significant differences were found for 90-day mRS 0–3, successful recanalization, sICH, or 90-day mortality (PROSPERO ID: CRD420251000352). Conflict of interest This study was supported by the Chengdu Medical Research Project (Grant No. 2025435). Lei Guo: nothing to disclose; Guo Tang: nothing to disclose; Yang Xiang: nothing to disclose; Quan Li: nothing to disclose; Chunling Li: nothing to disclose; Shu Yang: nothing to disclose; Neng-Wei Yu: nothing to disclose; Fu-Qiang Guo: nothing to disclose; Jun Zhang: nothing to disclose. Figure 1 - belongs to Background and aims Figure 2 - belongs to Methods Table 1 - belongs to Results
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