Surgery is a common approach for diffuse coronary artery disease. Saphenous vein grafts are frequently used but are characterized by degeneration and high incidence of failure at 10 years. Percutaneous coronary intervention is preferred over re-operation because of age, comorbidity and the diffusion of coronary artery disease. With the saphenous vein graft occluded, percutaneous coronary intervention of native vessels and medical therapy alone are commonly suggested. We report three cases of patients with totally occluded saphenous vein grafts with suitable characteristics for treatment with Proxis, a device able to induce a proximal protection of the target vessel, minimizing the risk of distal embolization as well as the quantity of contrast required. In all patients there were no complications or cardiac enzyme elevations, and each case resulted in complete revascularization immediately postprocedure. Patients were asymptomatic at 6-month follow-up and procedural success was shown in two patients that consented to follow-up angiography. We conclude that Proxis could be a valuable tool for percutaneous coronary intervention of totally occluded saphenous vein grafts in patients who are poor candidates for percutaneous coronary intervention of native vessel; nevertheless these observations should be confirmed by a long-term follow-up controlled study.