Resumen: To strengthen research ethics systemically, the Pan American Health Organization (PAHO) devised a strategy that includes objectives and indicators to address core components of research ethics systems. We assessed 22 countries in Latin America and the Caribbean using these indicators. Most countries have adopted legal instruments to govern research with human participants and have implemented national bodies tasked with the oversight of research ethics committees. However, performance with regard to ethics training policies and clinical trial registration was less advanced, and efforts to adopt policies on responsible conduct of research and accelerated ethics review of emergency research did not meet the PAHO objectives in most countries. We discuss the pending challenges and provide recommendations aimed at helping countries from Latin America and the Caribbean to achieve the indicators, and, more generally, to strengthen research ethics with a systemic approach.