Hypertension remains the most common modifiable cardiovascular risk factor, yet hypertension control rates remain dismal. Home blood pressure (BP) monitoring has the potential to improve hypertension control. The purpose of this review was to quantify both the magnitude and mechanisms of benefit of home BP monitoring on BP reduction. Using a structured review, studies were selected if they reported either changes in BP or percentage of participants achieving a pre-established BP goal between randomized groups using home-based and office-based BP measurements. A random-effects model was used to estimate the magnitude of benefit and relative risk. The search yielded 37 randomized controlled trials with 9446 participants that contributed data for this meta-analysis. Compared with clinic-based measurements (control group), systolic BP improved with home-based BP monitoring (-2.63 mm Hg; 95% CI, -4.24, -1.02); diastolic BP also showed improvement (-1.68 mm Hg; 95% CI, -2.58, -0.79). Reductions in home BP monitoring-based therapy were greater when telemonitoring was used. Home BP monitoring led to more frequent antihypertensive medication reductions (relative risk, 2.02 [95% CI, 1.32 to 3.11]) and was associated with less therapeutic inertia defined as unchanged medication despite elevated BP (relative risk for unchanged medication, 0.82 [95% CI, 0.68 to 0.99]). Compared with clinic BP monitoring alone, home BP monitoring has the potential to overcome therapeutic inertia and lead to a small but significant reduction in systolic and diastolic BP. Hypertension control with home BP monitoring can be enhanced further when accompanied by plans to monitor and treat elevated BP such as through telemonitoring.