In this episode, we compare hydrochlorothiazide and chlorthalidone, but specifically from a cardiovascular outcomes perspective when used in patients with hypertension. Key Concepts Chlorthalidone, hydrochlorothiazide, and indapamide are available thiazide diuretics for treatment of hypertension; however, hydrochlorothiazide is the most commonly used agent. Chlorthalidone is more potent in reducing blood pressure but also is associated with a higher risk of electrolyte abnormalities compared to HCTZ.  Recent studies for cardiovascular outcomes show that chlorthalidone is not better than HCTZ in preventing CV outcomes, but increases risk for hypokalemia, need for monitoring and even potassium supplementation.  References Ishani A, Cushman WC, Leatherman SM, et al. Chlorthalidone vs. Hydrochlorothiazide for Hypertension–Cardiovascular Events. N Engl J Med 2022; 387:2401-2410. DOI: 10.1056/NEJMoa2212270. https://www.nejm.org/doi/full/10.1056/NEJMoa2212270 Akbari P, Khorasani-Zadeh A. Thiazide Diuretics. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2023 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532918/