Introduction/Background: Acute limb ischemia (ALI) is a severe complication of peripheral artery disease. Lipid lowering and antithrombotic therapies reduce ALI but pathologic studies have described thrombus in distal arteries without plaque, suggesting that artery to artery embolism from proximal (aortic-iliac) athero-thrombosis may be a key driver. Research Questions/Hypothesis: We hypothesized that the burden and character of atherosclerosis in the iliac arteries of patients with PAD would be associated with long term risk of ALI. Methods: VOYAGER PAD enrolled 6,554 patients with PAD and collected 2,200 baseline angiograms in 1,664 patients including 400 CT angiograms enabling plaque characterization. A case-control of 9 who had ALI during follow up and 9 controls were matched on anatomic and patient characteristics, type of index revascularization and disease pattern. Images were read by a blinded, independent imaging core lab. Results/Data: Of the 9 ALI cases, 45% had iliac artery occlusion and 55% had distal artery occlusion. Plaque characteristics were different in cases relative to controls including significantly greater non-calcified plaque volume (OR 2.36, 95% CI 1.05 - 9.38, p=0.03) as well as similar trends for low attenuation plaque (OR 1.65, 95% CI 0.89 - 4.72, p=0.05), and plaque burden (OR 1.16, 95% CI 1.00 - 1.25, p=0.03, Figure). In patients who experienced ALI, there was a trend for greater non-calcified plaque in the limb that experienced the ALI relative to the contra-lateral limb (index 7.2 vs contra-lateral 5.4, p=0.08). Conclusions: In a case-control series, total non-calcified plaque volume and overall plaque burden in the iliac arteries were associated with future ALI over 3 years. Based on the observations in this case-control, we are now analyzing plaque and outcomes in the full cohort. These data are hypothesis generating and suggest that plaque characteristics may be associated with ALI and may serve a surrogate marker of risk.