ABSTRACT: Hypertension affects one third of the U.S. adult population. Although cost-effectiveness analyses of antihypertensive medicines have been published, a comprehensive systematic review across medicine classes is not available.PubMed, Embase, Cochrane Library, and Health Technology Assessment were searched to identify original cost-effectiveness analyses published from 1990 through August 2016. Results were summarized by medicine class: angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), thiazide-type diuretics, ?-blockers, and others. Incremental cost-effectiveness ratios (ICERs) were adjusted to 2015 U.S. dollars.Among 76 studies reviewed, 14 compared medicines with no treatment, 16 compared medicines with conventional therapy, 29 compared between medicine classes, 13 compared within medicine class, and 11 compared combination therapies. All antihypertensives were cost effective compared with no treatment (ICER/quality-adjusted life year [QALY]=dominant-$19,945). ARBs were more cost effective than CCBs (ICER/QALY=dominant-$13,016) in nine comparisons, whereas CCBs were more cost effective than ARBs (ICER/QALY=dominant) in two comparisons. ARBs were more cost effective than ACEIs (ICER/QALY=dominant-$34,244) and ?-blockers (ICER/QALY=$1,498-$18,137) in all eight comparisons.All antihypertensives were cost effective compared with no treatment. ARBs appeared to be more cost effective than CCBs, ACEIs, and ?-blockers. However, these latter findings should be interpreted with caution because these findings are not robust due to the substantial variability across the studies, including study settings and analytic models, changes in the cost of generic medicines, and publication bias.