From the Guidelines

Chlorthalidone is generally more effective than hydrochlorothiazide for blood pressure control, despite both being thiazide-type diuretics.

Chlorthalidone has a longer duration of action (24-72 hours versus 6-12 hours for hydrochlorothiazide), allowing for once-daily dosing and providing more consistent 24-hour blood pressure control 1.
Typical dosing for chlorthalidone is 12.5-25 mg once daily, while hydrochlorothiazide is usually prescribed at 12.5-50 mg daily.
Chlorthalidone has demonstrated superior outcomes in reducing cardiovascular events in clinical trials, likely due to its longer half-life and more potent blood pressure-lowering effects 1.

Chlorthalidone may cause more electrolyte abnormalities, particularly hypokalemia, hyponatremia, and hypercalcemia, requiring closer monitoring of electrolytes 1.
Both medications have similar side effect profiles otherwise, including glucose intolerance, hyperuricemia, and photosensitivity.

When switching from hydrochlorothiazide to chlorthalidone, a dose conversion of approximately 2:1 is often used (25 mg hydrochlorothiazide is roughly equivalent to 12.5 mg chlorthalidone) 1.

The choice between chlorthalidone and hydrochlorothiazide should be based on individual patient factors, including the presence of kidney disease, heart failure, and other comorbidities 1.
Clinicians should carefully monitor patients for signs of electrolyte imbalance and adjust treatment accordingly 1.

From the Research

Chlorthalidone and hydrochlorothiazide (HCTZ) are both thiazide diuretics used to treat hypertension, but their effectiveness and safety profiles have been compared in several studies 2, 3, 4, 5.
A study published in 2020 found that chlorthalidone was not associated with significant cardiovascular benefits compared to HCTZ, but was associated with a greater risk of renal and electrolyte abnormalities, such as hypokalemia and hyponatremia 2.
Another study published in 2013 found that chlorthalidone was not associated with fewer adverse cardiovascular events or deaths than HCTZ in older adults, but was associated with a greater incidence of electrolyte abnormalities, particularly hypokalemia 3.
A 2006 study found that chlorthalidone was more effective in lowering systolic blood pressure than HCTZ, as evidenced by 24-hour ambulatory blood pressure monitoring 4.
A 2010 review of the literature found that both chlorthalidone and HCTZ were effective in lowering blood pressure, but that chlorthalidone may have a more favorable profile in terms of reducing clinical complications of hypertension, although the evidence was not conclusive 5.
A 2024 article reviewed recent studies and found that chlorthalidone is recommended over HCTZ as the preferred diuretic for patients with primary hypertension due to its greater reduction of major adverse cardiovascular events (MACE) 6.

The safety and efficacy of chlorthalidone and HCTZ have been compared in several studies, with mixed results 2, 3, 4, 5.
Chlorthalidone has been associated with a greater risk of hypokalemia and hyponatremia compared to HCTZ 2, 3.
HCTZ has been associated with a greater risk of abnormal weight gain compared to chlorthalidone 2.
The efficacy of chlorthalidone and HCTZ in lowering blood pressure has been compared in several studies, with some studies finding that chlorthalidone is more effective 4.