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Introduction: Preeclampsia, a common pregnancy complication, has been associated with impaired cardiac function and coronary artery disease in the adult offspring. Hypercholesterolemia (HC) is a significant risk factor for cardiovascular disease (CVD). However, during pregnancy, HC is required for normal fetal development. In contrast, excessive HC in pregnancy is associated with the development of preeclampsia, but the impact of excessive pregnancy-specific HC on offspring cardiovascular function is not known. We hypothesized that exposure to excessive HC in pregnancy impairs cardiac and vascular function in the adult offspring. Methods: Sprague-Dawley rats were fed a control diet (CD) or a high cholesterol diet (HCD) only from gestational day (GD) 6 to 20 (term=GD22). Male and female offspring were aged to 4 months (adulthood). In isolated hearts, cardiac susceptibility to ischemia/reperfusion insult (I/R; 20 min ischemia/ 40 min reperfusion) was assessed ex vivo using the isolated working heart technique. Percent cardiac recovery compared to baseline was calculated. In addition, cardiac left ascending coronary arteries were isolated, and endothelium-dependent vasodilation responses to methylcholine (MCh) and vasoconstrictor capacity to a thromboxane A2 agonist (U46619) were assessed by wire myography. Vascular function data were summarized as area under the curve (arbitrary units, a.u.). Male and female data (means±SEM) were analyzed by unpaired Student's t-test; p≤0.05 was considered significant; n=3-10/group. Results: In the adult male offspring, HCD in pregnancy decreased the cardiac recovery from I/R compared to CD offspring (CD: 21.57.3 vs HCD: 4.31.3%; p=0.05). Moreover, coronary artery responsiveness to MCh was reduced in HCD compared to CD male offspring (CD: 382.210.3 vs 333.210.0 a.u.; p=0.005), without changes in U46619 vasoconstriction. In contrast, in the adult female offspring, exposure to HCD in pregnancy did not impact the cardiac recovery from I/R, or vasorelaxation or vasoconstriction responses in coronary arteries, compared to control female offspring. Conclusions: In male offspring, exposure to excessive maternal HC in pregnancy reduced the cardiac capacity to recovery from I/R insult, which may be, in part, mediated via the impaired endothelium-dependent vasodilation in the coronary arteries. In contrast, the adult female offspring, exposure to HC in pregnancy did not impact cardiac or coronary artery function. It has been estimated that >25% of women develop excessive HC in pregnancy, yet there is a paucity of data on the impact on offspring health. These results expand our knowledge of the sex-specific differences in an understudied susceptible population of children at risk of later-life CVD, allowing for an opportunity to diagnose and develop early intervention strategies.