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Background: Cardiovascular disease (CVD) morbidity and mortality is increasing in Africa, largely due to undiagnosed and untreated hypertension. Approaches that leverage existing primary health systems could improve hypertension treatment and reduce CVD, but cost-effectiveness is unknown. We evaluated the cost-effectiveness of population-level hypertension screening and implementation of chronic care clinics across eastern, southern, central, and western Africa. Methods and findings: We conducted a modeling study to simulate hypertension and CVD across 3,000 scenarios representing a range of settings across eastern, southern, central, and western Africa. We evaluated 2 policies compared to current hypertension treatment: (1) expansion of HIV primary care clinics into chronic care clinics that provide hypertension treatment for all persons regardless of HIV status (chronic care clinic or CCC policy); and (2) CCC plus population-level hypertension screening of adults ≥40 years of age by community health workers (CHW policy). For our primary analysis, we used a cost-effectiveness threshold of US $500 per disability-adjusted life-year (DALY) averted, a 3% annual discount rate, and a 50-year time horizon. A strategy was considered cost-effective if it led to the lowest net DALYs, which is a measure of DALY burden that takes account of the DALY implications of the cost for a given cost-effectiveness threshold. Among adults 45 to 64 years, CCC implementation would improve population-level hypertension control (the proportion of people with hypertension whose blood pressure is controlled) from mean 4% (90% range 1% to 7%) to 14% (6% to 26%); additional CHW screening would improve control to 44% (35% to 54%). Among all adults, CCC implementation would reduce ischemic heart disease (IHD) incidence by 10% (3% to 17%), strokes by 13% (5% to 23%), and CVD mortality by 9% (3% to 15%). CCC plus CHW screening would reduce IHD by 28% (19% to 36%), strokes by 36% (25% to 47%), and CVD mortality by 25% (17% to 34%). CHW screening was cost-effective in 62% of scenarios, CCC in 31%, and neither policy was cost-effective in 7% of scenarios. Pooling across setting-scenarios, incremental cost-effectiveness ratios were $69/DALY averted for CCC and $389/DALY averted adding CHW screening to CCC. Conclusions: Leveraging existing healthcare infrastructure to implement population-level hypertension screening by CHWs and hypertension treatment through integrated chronic care clinics is expected to reduce CVD morbidity and mortality and is likely to be cost-effective in most settings across Africa. Matthew Hickey and colleagues report the results of a modelling study that indicates that leveraging existing healthcare infrastructure to implement population-level hypertension assessment and treatment could be cost effective. Author summary: Why was this study done?: Cardiovascular disease (CVD), such as heart attacks and strokes, are increasingly causing illness and death in Africa, mainly due to undiagnosed and untreated hypertension. Hypertension is currently treated primarily in specialized clinics; existing primary health systems, particularly those developed for HIV care, could potentially be used to treat hypertension more effectively. Prior research also demonstrates that community health workers can successfully conduct hypertension screening in the community, improving both diagnosis and linkage to care. This research aimed to determine whether integration of hypertension care within existing primary health systems with or without community health worker screening of all adults aged 40 or greater in the community for hypertension would be a worthwhile investment in Africa. What did the researchers do and find?: We incorporated hypertension and CVD into an existing individual-level HIV model and simulated hypertension and CVD outcomes across 3,000 scenarios in eastern, southern, central, and western Africa. We evaluated 2 policies compared to current standard hypertension care: expanding primary care clinics to include HIV and hypertension (chronic care clinic or CCC policy) and adding community health worker (CHW) screening for all adults over 40 years of age. For all adults, CCC would reduce heart attacks by 10%, strokes by 13%, and cardiovascular deaths by 9%, while adding CHW screening would reduce these by 28%, 36%, and 25%, respectively. CHW screening was cost-effective in 62% of scenarios, CCC in 31%, and neither policy was considered cost-effective in 7% of scenarios. What do these findings mean?: Using existing primary health care and community health worker infrastructure to screen and treat hypertension can significantly reduce illness and death from CVD in Africa. Implementing chronic care clinics and community health worker screenings for hypertension is likely to be cost-effective in most settings. These findings support policy changes to integrate hypertension management into existing primary health services to improve CVD prevention. Though we considered numerous factors in our model, findings are limited by uncertainty in model parameters, inability to include all potential policy alternatives, and uncertainty around how the current state of hypertension care will evolve in the future. [ABSTRACT FROM AUTHOR]