The causal relationship between obesity and high blood pressure is established; however, the detailed pathways for such association are still under research. This work aims to assess the changes in neprilysin, vasoconstrictor, and vasodilatory molecules in obese hypertensive patients undergoing laparoscopic sleeve gastrectomy (LSG).The present prospective study was done on 59 hypertensive obese patients in whom LGS was performed. Blood pressure, as well as blood samples for neprilysin, angiotensinogen, angiotensin II, renin, endothelin-1 "ET-1', aldosterone, atrial natriuretic peptide "ANP,' and B-type natriuretic peptide 'BNP," were assessed before and 15 months after surgery. Patients were divided into two groups according to the remission of hypertension (HTN).After 15 months, remission of hypertension was seen in 42 patients (71%). The declines in the following measurements were significantly higher in patients with remission than those with persistent HTN: aldosterone (P=0.029567), angiotensin II (P < 0.000001), angiotensinogen (P = 0.000021), neprilysin (P = 0.000601), renin (P = 0.000454) and endothelin 1(P = 0.000030). There was a significantly higher increment in ANP (P = 0.000002) and a nonsignificant increment in BNP (P=0.081740). Angiotensin II 15 months after LSG and Δ ANP % were significant independent predictors of persistent HTN.In the setting of LSG, aldosterone, angiotensinogen, angiotensin II, renin, and neprilysin were significantly lower in patients with remission of HTN after 15 months than those with persistent HTN, and natriuretic peptides were significantly higher. A lower postoperative level of angiotensin II and a larger percent increment of ANP are independently associated with hypertension remission after LSG.