In spite of developments in interventional cardiology, the success rate of saphenous vein graft stenting is still low in patients with acute coronary syndromes. In this study, we aimed at finding out the effect of pretreatment with Tirofiban, a glycoprotein IIb/IIIa inhibitor, and clopidogrel, an adenosine diphosphate antagonist, on the outcome of saphenous vein graft stenting in patients with acute coronary syndrome. A total of 47 patients, who had lesions in saphenous vein grafts and acute coronary syndrome, could be randomized to treated group (n = 24), who received Tirofiban and clopidogrel for 48 hours before the intervention, and untreated group (n = 23), who did not receive Tirofiban and clopidogrel. In the untreated group, the intervention was performed just after the coronary angiography. All patients underwent stenting as the standard intervention. The groups were compared by Mann-Whitney's U-test or Chi-Square test. The level of statistical significance was set at 0.05. There were no significant differences regarding age, gender, and atherosclerotic risk factors between the two groups. In treated group, precutaneous coronary intervention was successful in all patients and no-reflow phenomenon occurred in only one patient. The rate of no-reflow or slow-flow phenomenon was significantly lower in treated group (one patient vs 9 patients, p = 0.004). One patient in untreated group experienced ventricular fibrillation, which was converted to sinus rhythm after defibrillation. During short-term follow-up, there were no acute myocardial infarction, coronary bypass surgery or death in both groups. There was no major bleeding. Minor bleeding was more frequent in treated group, but it did not achieve statistical significance (3 vs 1; p = 0.322). In conclusion, pretreatment with tirofiban and clopidogrel before percutaneous coronary intervention might result in better immediate outcomes in old saphenous vein grafts without any significant increase in bleeding complications.