A diet consisting of high levels of saturated fat has been linked to a dramatic rise in obesity, type II diabetes, and metabolic syndrome. The effect of these co-morbidities on stroke outcome has not been examined in detail in human or animal studies. In this study we hypothesized that maintaining animals on a high fat, "Western diet" (WD), for an extended period would have a detrimental effect on ischemic outcome. Forty-eight male Sprague-Dawley rats were exposed to 1 month of either WD or control diets initiated at 6 weeks of age (Experiment 1) or 3 months of either WD or control diets initiated at 4 weeks of age (Experiment 2) prior to endothelin-1-induced ischemia. Following ischemia, animals were assessed in the staircase reaching and beam-traversing tests at 2 and 4 weeks post-ischemia and infarct volumes were calculated at 4 weeks post-ischemia. Analysis revealed no difference between animals exposed to either WD or control diets for 1 month in behavioral or histological assessments. In contrast, 3 months of WD diet exposure significantly increased functional impairments in both the staircase and beam-traversing tests as well as increasing the volume of infarction, primarily in the cortex. The results of this study demonstrate that long-term exposure to WD diets are detrimental to ischemic outcome. Consequently, it is important to incorporate disease co-morbidities and/or risk factors in pre-clinical evaluation of neuroprotective or restorative interventions if therapies are to be translated into the clinic. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.