The World Health Organization (WHO) launched the Global Hearts Initiative and its HEARTS Technical Package in 2016. Its aim is to improve clinical preventive services in primary health care (PHC) using highly effective, scalable, sustainable, and proven interventions. As the WHO Regional Office for the Americas, the Pan American Health Organization (PAHO) is developing and coordinating the HEARTS in the Americas Initiative with a clear vision: By 2025, HEARTS will be the institutionalized model for cardiovascular disease risk management, including hypertension, diabetes, and dyslipidemia in primary health care in the Americas.The HEARTS in the Americas Initiative is entering its sixth year of implementation, having expanded from the original cohort of 4 countries to 22 current countries implementing the HEARTS model. The accumulation of knowledge, practices, and experiences from the field and from different levels of implementation has been compiled in this new Guide and Essentials for Implementation. This manual complements the WHO HEARTS technical package Implementation Guide. Expanding on specific lessons learned from the systematic implementation of HEARTS in the Americas as it spans various roles and requires coordination across ministry of health (MOH) departments, stakeholders, partner agencies, scientific societies, and academic institutions. Documenting the implementation and scale-up experiences of countries in the Americas is timely to propel forward the institutionalization of the HEARTS model for cardiovascular disease (CVD) risk management, including hypertension, diabetes, and dyslipidemia in PHC in the Americas by 2025. This manual is designed to be practical and user-friendly. It aims to guide implementers at national and subnational levels to navigate throughout different stages of implementation and to ensure longtime sustainability. The manual is written for national focal points, managers and coordinators at subregional, provincial, district, municipal level, and health facilities implementing HEARTS. It is intended to answer frequently asked questions about the premises, objectives, components, and steps for implementation of the HEARTS in the Americas Initiative.