Objectives <p>Intravascular ultrasound (IVUS)-guided revascularization offers clinical benefits compared to angiography-guided revascularization in patients with femoropopliteal occlusive disease. This study evaluates the cost-effectiveness of IVUS-guided versus angiography-guided revascularization from a Spanish payer perspective.</p> Methods <p>A cost-effectiveness model combining a short-term decision tree and a long-term semi-Markov structure was developed to simulate clinical outcomes and costs over a lifetime horizon from the Spanish perspective. Transition probabilities, costs, and utility weights for health states including reintervention, amputation and death were derived from published literature and Spanish national databases. Health outcomes were measured in quality-adjusted life-years (QALYs), and costs were reported in 2025 Euros. One-way and probabilistic sensitivity analyses were conducted to assess model robustness.</p> Results <p>IVUS-guided revascularization was associated with improved clinical outcomes and reduced lifetime costs, dominating angiography-guided revascularization. In the base case, IVUS yielded 0.29 additional lifetime QALYs and €3,289 in lifetime cost savings per patient compared with angiography, resulting in a dominance of IVUS. Scenario analysis assuming equal amputation risk still favored IVUS. One-way sensitivity analysis identified the reintervention risk and costs as key drivers, and probabilistic sensitivity analysis confirmed that IVUS dominated in over 90% of simulations.</p> Conclusion <p>IVUS-guided revascularization is a cost-effective strategy for femoropopliteal occlusive disease in Spain, offering superior clinical outcomes and economic efficiency. These findings support broader adoption of IVUS in peripheral interventions.</p>