The authors prospectively evaluated 387 consecutive patients with proliferative diabetic retinopathy (PDR) for asymmetry in posterior segment neovascularization and its relationship to carotid artery disease. For the purpose of this study, asymmetry is defined as the presence of PDR with high-risk characteristics (as per the Diabetic Retinopathy Study) in one eye, with neither proliferative nor preproliferative changes in the opposite eye. Over the 2-year time period of the study, 20 (5.2%) of 387 patients manifested asymmetric PDR by this definition. All 20 patients underwent carotid artery noninvasive testing and 4 (20%) were found to have hemodynamically significant carotid artery disease. Two of the four patients had their proliferative retinopathy ipsilateral to their severe carotid artery stenosis. This finding does not support the hypothesis that a hemodynamically significant carotid artery stenosis protects against the development of PDR.