Summary: The current review summarizes the current place of single pill combination of walsartan and indapamide SR in the treatment of hypertension in patients with high or very high cardiovascular risk. Among several beneficial effects on CV system , brain and kidney – walsartan, AT-1 receptor antagonist with multiple faces in the treatment of hypertension, reduces albuminuria more than other BP-lowering drugs, is effective at delaying the progression of diabetic and non-diabetic CKD, prevents or regresses HMOD and are is particularly recommended in those patients with high cardiovascular risk. Indapamide SR have a longer duration of action compared with hydrochlorothiazide. A meta-analysis of placebo-controlled studies based on thiazides, chlorthalidone, and indapamide found similar effects for the three types of diuretics on CV outcomes A greater risk of CV events and HF has been reported with thiazide diuretics as compared to indapamide in another meta-analysis The above-mentioned recent observations justify the recommendation of the present 2023 ESH guidelines to still consider indapamid as a suitable antihypertensive agent and as similarly effective in CV prevention.