Obesity, particularly abdominal obesity, is associated with increased risks of arterial hypertension, diabetes mellitus, hyperlipidemia, sleep apnea, coronary artery disease, stroke and mortality. Weight loss surgery is the most effective treatment for morbid obesity, mainly because medical and dietary treatments have been proven insufficient in the long run. Our primary end point was to study the gender effect on vascular responsiveness (endothelial function and the ankle brachial index [ABI]) 3 months post bariatric surgery. Our secondary end points were to study the effect of gender on antropometric parameters (BMI, waist circumference) and chronic diseases (diabetes mellitus type II, arterial hypertension) 3 months following bariatric surgery, and to find independent variables that may affect and predict the post-operative clinical outcome. Methods: In this prospective study, patients were evaluated one day before surgery and 3 months afterwards. Ankle brachial index was measured while the patient was supine after 15 minutes rest and measurement of the systolic blood pressure in all four extremities was done. The brachial artery method was used to measure endothelial function expressed as flow mediated diameter percent change (FMD %). FMD% more than 10% is considered a normal response. Results: Compared with diabetic females, diabetic males had a higher postoperative BMI (men with diabetes mellitus did not lose weight as much as diabetic women) (β=-0.299; P=0.04), while women with diabetes mellitus had a more significant reduction in BMI postoperatively (β=+0.287; P=0.04). Following bariatric surgery, 12 of the 21 patients with diabetes mellitus type II did not need any medications for diabetes (kept HbA1c% less than 6.5%). All other diabetic patients improved their diabetes mellitus status. Women significantly improved their ABI (average increase of 0.07, p=0.04) and their endothelial function (FMD% change was improved from -3.5±9.0% to 14.8±8.1%, an improvement of 18.3%, p<0.001). Systolic blood pressure was decreased significantly (by 6.6 mmHg, p=0.04). Men improved their endothelial function (FMD% change was improved from -1.3±10.1% to 11.7±6.2%, p<0.001), but no significant change was observed in systolic blood pressure (p=0.29) nor in ABI (P=0.8). A linear regression analysis found that a higher baseline FMD% significantly predicted a higher postoperative FMD% (β=0.294, P=0.03). In obese males, the higher the baseline BMI the worse the post operative endothelial function (β=-0.921, Pd<0.001) and the same adverse effect was documented for hypertensive men (β=-0.380, P=0.05). For females, the higher the baseline FMD% the higher the postoperative FMD% (β=+0.397; P=0.01) [a favorable outcome]. Discussion: Our study has demonstrated a possible mechanistic insight into gender effects observed in epidemiological studies through improvement in vascular response in females undergoing this operation including a better reduction in systolic blood pressure and a better weight reduction in diabetic women with improvement in ABI; unlike males, who did not improve their ABI and did not decrease systolic blood pressure, and the finding that obese diabetic males and obese hypertensive males did the worst.