Background The prevalence of hypertension is high and increasing worldwide while the proportion of controlled hypertension is low. Purpose To assess the comparative effectiveness of 8 implementation strategies for blood pressure (BP) control in adults with hypertension. Data Sources Systematic searches of MEDLINE and Embase from inception to September 2017 with no language restriction supplemented with manual reference searches. Study Selection Randomized controlled trials lasting at least 6 months comparing implementation strategies versus usual care on BP reduction in adults with hypertension. Data Extraction Two investigators independently extracted trial data. Trials were grouped by implementation strategy, and BP reduction effects were compared using multivariate-adjusted generalized estimating equations. A modified Cochrane Risk of Bias tool was used for trial quality assessment. Data Synthesis A total of 121 comparisons from 100 articles with 55,920 hypertensive patients were included. Multilevel, multicomponent strategies, such as team-based care with medication titration by non-physician [−7.1 mmHg (95% CI: −8.9, −5.2)], team-based care with medication titration by physician [−6.2 mmHg (−8.1, −4.2)], and multilevel strategies without team-based care [−5.0 mmHg (−8.0, −2.0)] were most effective for systolic BP reduction. Patient-level strategies also resulted in significant systolic BP reductions of −3.9 mmHg (−5.4, −2.3) for health coaching and −2.7 mmHg (−3.6, −1.7) for home BP monitoring. Similar trends were observed for diastolic BP reduction. Provider training was tested in few trials and resulted in non-significant BP reduction. Limitations Sparse data from low- and middle-income countries, few trials of some implementation strategies, and possible publication bias. Conclusions Multilevel, multicomponent strategies, followed by patient-level strategies, are most effective for BP control in patients with hypertension and ought to be used to improve hypertension control. Primary Funding Source US National Institutes of Health