Left ventricular hypertrophy develops in 36%‐41% of hypertensive patients and independently predicts cardiovascular events and total mortality. Moreover, drug‐induced reduction in left ventricular mass (LVM) correlates with improved prognosis. The optimal thiazide‐type diuretic for reducing LVM is unknown. Evidence regarding potency, cardiovascular events, sodium, and potassium suggested the hypothesis that “CHIP” diuretics (CHlorthalidone, Indapamide, and Potassium‐sparing diuretic/hydrochlorothiazide [PSD/HCTZ]) would reduce LVM more than HCTZ. Systematic searches of five databases were conducted. Among the 38 randomized trials, a 1% reduction in systolic blood pressure (SBP) predicted a 1% reduction in LVM, P = 0.00001. CHIP‐HCTZ differences in reducing LVM differed across trials (ie, heterogeneity), making interpretation uncertain. However, among the 28 double‐blind trials, heterogeneity was undetectable, and HCTZ reduced LVM (percent reduction [95% CI]) by −7.3 (−10.4, −4.2), P < 0.0001. CHIP diuretics surpassed HCTZ in reducing LVM: chlorthalidone −8.2 (−14.7, −1.6), P = 0.015; indapamide −7.5 (−12.7, −2.3), P = 0.005; and all CHIP diuretics combined −7.7 (−12.2, −3.1), P < 0.001. The comparison of PSD/HCTZ with HCTZ had low statistical power but favored PSD/HCTZ: −6.0 (−14.1, +2.1), P = 0.149. Thus, compared to HCTZ, CHIP diuretics had twice the effect on LVM. CHIP diuretics did not surpass HCTZ in reducing systolic or diastolic blood pressure: −0.3 (−5.0, +4.3) and −1.6 (−5.6, +2.4), respectively. The strength of evidence that CHIP diuretics surpass HCTZ for reducing LVM was high (GRADE criteria). In conclusion, these novel results have demonstrated that CHIP diuretics reduce LVM 2‐fold more than HCTZ among hypertensive patients. Although generally related to LVM, blood pressure fails to explain the superiority of CHIP diuretics for reducing LVM.