Hydrochlorothiazide, sold under the brand name Hydrodiuril among others, is a diuretic medication used to treat hypertension and swelling due to fluid build-up. Other uses include treating diabetes insipidus and renal tubular acidosis and to decrease the risk of kidney stones in hypercalciuria. Hydrochlorothiazide is taken by mouth and may be combined with other blood pressure medications as a single pill to increase effectiveness. Hydrochlorothiazide is a thiazide medication which inhibits reabsorption of sodium and chloride ions from the distal convoluted tubules of the kidneys, causing a natriuresis. This initially increases urine volume and lowers blood volume. It is believed to reduce peripheral vascular resistance.

Potential side effects include poor kidney function, electrolyte imbalances, including low blood potassium, and, less commonly, low blood sodium, gout, high blood sugar, and feeling lightheaded with standing.

Two companies, Merck & Co. and Ciba Specialty Chemicals, state they discovered the medication which became commercially available in 1959. It is on the World Health Organization's List of Essential Medicines. It is available as a generic drug and is relatively affordable. In 2023, it was the sixteenth most commonly prescribed medication in the United States, with more than 31 million prescriptions.

Hydrochlorothiazide is a thiazide diuretic.

Hydrochlorothiazide inhibits sodium reabsorption in the distal convoluted tubules, leading to increased excretion of sodium and water, along with potassium and hydrogen ions. This diuretic action reduces plasma volume, decreases cardiac output, and lowers blood pressure.

Hydrochlorothiazide is used for the treatment of hypertension, congestive heart failure, symptomatic edema, diabetes insipidus, renal tubular acidosis. It is also used for the prevention of kidney stones in those who have high levels of calcium in their urine.

Multiple studies suggest hydrochlorothiazide could be used as initial monotherapy in people with primary hypertension; however, the decision should be weighed against the consequence of long-term adverse metabolic abnormalities. Doses of hydrochlorothiazide of 50 mg or less over four years reduced mortality and development of cardiovascular diseases better than high-dose hydrochlorothiazide (50 mg or more) and beta-blockers. A 2019 review supported equivalence between drug classes for initiating monotherapy in hypertension, although thiazide or thiazide-like diuretics showed better primary effectiveness and safety profiles than angiotensin-converting enzyme inhibitors and non-dihydropyridine calcium channel blockers.

Low doses (50 mg or less) of hydrochlorothiazide as first‐line therapy for hypertension were found to reduce total mortality and cardiovascular disease events over a four-year study. Hydrochlorothiazide appears be more effective than chlorthalidone in preventing heart attacks and strokes. Hydrochlorothiazide is less potent but may be more effective than chlorthalidone in reducing blood pressure. More robust studies are required to confirm which drug is superior in reducing cardiovascular events. Side effect profile for both drugs appear similar and are dose dependent.