Acute ischemic stroke (AIS) is a leading cause of long-term disability and mortality worldwide, necessitating the rapid implementation of time-sensitive reperfusion therapies to improve outcomes. The "drip and ship" (DS) model, in which intravenous thrombolysis (IVT) is initiated at a primary stroke center (PSC) followed by transfer for endovascular thrombectomy (EVT) at a comprehensive stroke center, is widely adopted, particularly in regions with limited immediate EVT access. This narrative review synthesizes evidence from randomized-controlled clinical trials, large-scale observational registries, meta-analyses, and expert-consensus statements to comprehensively analyze the DS model in AIS management, compare it with the mothership (MS) paradigm, and evaluate current evidence regarding workflow optimization, pharmacologic strategies, and system-level innovations. Evidence comparing DS and MS models highlights the complexity of balancing early IVT with minimizing delays to EVT, with regional factors influencing the optimal approach. Reducing door-in-door-out times is critical within DS pathways, as prolonged interhospital transfer is associated with worse outcomes, emphasizing the need for streamlined protocols, prehospital notification, and telemedicine integration. Bridging therapy with IVT, particularly using tenecteplase, is associated with improved rates of early recanalization, supporting its continued use within DS workflows. Emerging adjunctive therapies offer potential for enhancing arterial recanalization and microcirculatory reperfusion without delaying transfer. The "drive-the-doctor" paradigm, involving the transfer of neurointerventionalists to PSCs, may further reduce onset-to-reperfusion times in geographically challenging settings. Mobile stroke units, equipped with CT imaging and telemedicine capabilities, represent an additional strategy to initiate IVT in the field while expediting triage decisions for EVT. Collectively, these advancements support the continued refinement of the DS model, emphasizing the need for structured system-level improvements to optimize timely reperfusion and functional recovery in AIS patients. Continued research is necessary to further define optimal strategies within the DS framework to ensure equitable and effective stroke care across diverse healthcare environments.

1st Department of Neurology St Anne's University Hospital Brno Faculty of Medicine Masaryk University Brno Czech Republic

2nd Department of Neurology AHEPA University Hospital School of Medicine Aristotle University of Thessaloniki Thessaloniki Greece

2nd Department of Neurology Attikon University Hospital School of Medicine National and Kapodistrian University of Athens Athens Greece

2nd Department of Neurology Attikon University Hospital School of Medicine National and Kapodistrian University of Athens Rimini 1 Chaidari Athens 12462 Greece

Department of Biotechnological and Applied Clinical Sciences University of L'Aquila L'Aquila Italy

Department of Neurology GHU Paris Psychiatrie et Neurosciences Paris France

Department of Neurology University Hospital Basel University of Basel Basel Switzerland

Department of Neurology University Hospitals Cleveland Medical Center Cleveland OH USA

Department of Neurology University of Tennessee Health Sciences Center Memphis TN USA

Institute of Psychiatry and Neuroscience of Paris INSERM U1266 Université Paris Cité Paris France

Neurology and Stroke Unit Department of Neurosciences Bufalini Hospital Cesena Italy

Neurology Department Hôpital Fondation A de Rothschild Paris France

Neurosurgery Semmes Murphey Foundation Memphis TN USA

Stroke Center Lisbon Central University Hospital ULS São José and Faculdade de Medicina Universidade de Lisboa Lisbon Portugal

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