The consumption of high levels of saturated fat over the course of several weeks may lead to exaggerated cardiovascular reactivity. The consumption of a single high-fat meal has been associated with a transient impairment of vascular function. In a randomized, repeated measures, crossover study we tested whether the consumption of a single high-fat meal by healthy, normotensive participants would affect cardiovascular reactivity when compared with an isocaloric, low-fat meal. Thirty healthy participants ate a high-fat (42 g) and a low-fat (1 g) meal on 2 separate occasions, and their cardiovascular response to 2 standard laboratory stressors was measured. Systolic blood pressure, diastolic blood pressure, and total peripheral resistance were greater in participants following the consumption of the high-fat meal relative to the low-fat meal. The findings of the present study are consistent with the hypothesis that even a single high-fat meal may be associated with heightened cardiovascular reactivity to stress and offer insight into the pathways through which a high-fat diet may affect cardiovascular function.