Distal balloon occlusion was approved as a means of embolic protection during saphenous vein graft intervention based on its ability to decrease major adverse clinical events (MACEs) by 42% in the 801-patient Saphenous Vein Graft Angioplasty Free of Emboli Randomized (SAFER) trial. However, the cost and technical complexity of this device have limited its widespread use and prompted some to avoid its use in cases that appear at "low risk" for complications. If predictors of MACEs and their potential decrease by distal balloon occlusion could be identified, this would have important clinical implications in this challenging population. We therefore used standard demographic and angiographic variables and 2 new angiographic markers (extent of graft degeneration and estimated volume of plaque in the target lesion) to construct multivariable logistic regression models of 30-day of MACEs in the SAFER trial. Independent correlates of increased 30-day MACEs were more extensive vein graft degeneration (p = 0.0001) and bulkier lesions (larger estimated plaque volume, p = 0.0005). Use of a distal balloon occlusion device was independently predictive of lower 30-day rates of MACE (p = 0.01), with uniform benefit across risk strata (no significant interaction between device use and independent angiographic risk factors). Thus, the risk of 30-day MACEs after percutaneous intervention in aortocoronary saphenous vein grafts is increased in more diffusely diseased grafts and in bulkier lesions, but a significant benefit of the GuardWire was seen across all levels of MACE risk rather than just those perceived to be at highest risk.