Diets high in fat are associated with vascular dysfunction. Frequent snacking may exacerbate this problem by extending the postprandial state. We hypothesized that repeated fat-rich mixed snacks would impair peripheral endothelial function and increase oxidative stress, a purported causal factor. Second, we hypothesized that feeding a quantity of snack based on the subject's body size would not cause different effects from feeding a fixed or constant size snack. A crossover design was used where 10 healthy males followed 2 repeated-snack regimens (fixed and variable based on body surface area), 1 week apart. Each regimen consisted of 2 snacks, fed 4 hours apart (0 and 4 hours). Markers of vascular function (reactive hyperemia index [RHI]), oxidative stress, and antioxidant capacity were measured before and after each snack. Peripheral vascular function improved from fasting to 2 hours after snack 1 (RHI2h-0h, P = .010), but the change before and after snack 2, RHI6h-4h, was negative (P = .026), indicating reduced endothelial function after repeated snacking. The oxidative stress marker changed over time (P = .043), increasing after snack 1 and decreasing before snack 2, with no change after snack 2. The antioxidant marker increased 2 hours after each snack (P = .003). Responses to fixed snacks over time were not different from variable snacks, although power was low; the effect size was large for antioxidant capacity, medium for oxidative stress, and small for RHI. Snacking after fasting resulted in a transiently improved peripheral vascular response that disappeared with a second snack. Antioxidant capacity appeared to help limit oxidative stress from repeated snacking in these healthy male subjects. (c) 2012 Elsevier Inc. All rights reserved.