OBJECTIVES:  To assess the cost-effectiveness of mechanical thrombectomy using a stent retriever and intravenous tissue plasminogen activator (IV t-PA) compared with IV t-PA alone in patients with acute ischemic stroke due to large vessel occlusion in Spain. METHODS:  A Markov state transition model defined by the modified Rankin Scale score was developed to estimate health outcomes expressed as life years gained and quality adjusted life years (QALY), and costs over patients’ lifetime. The model presents an acute phase (0-90 days) and a rest of life phase (90+ days). The analysis was conducted from the Spanish National Health System perspective and a 3% discount rate was applied to health outcomes and direct medical costs. Clinical inputs were based on the SWIFT PRIME clinical trial. Resource utilization and utilities were obtained from available published data and endorsed by an expert panel. Costs were obtained from different Spanish sources and expressed in € 2016. Deterministic and probabilistic sensitivity analyses were performed to examine the robustness of the results. RESULTS:  Stent-retriever thrombectomy after IV t-PA was associated with increased life years and QALYs gained (1.17 and 2.51, respectively) and with decreased costs of €44,378, resulting in the combined therapy being dominant over IV t-PA alone. A net monetary benefit of €119,744 was obtained considering a willingness-to-pay threshold of €30,000/QALY gained in the Spanish setting. The combined therapy was also dominant in all sensitivity analyses, deterministic and probabilistic. CONCLUSIONS: The present evaluation results in stent-retriever thrombectomy after IV t-PA being dominant over IV t-PA alone, meaning that it represents a more effective and less costly alternative compared to IV t-PA alone in the treatment of acute ischemic stroke patients in the Spanish setting.