A live, virtual conference, “Driving Responsible Conduct of Research during a Pandemic,” was held in April 2021, 13 months after the COVID-19 pandemic fundamentally altered the conduct of clinical research across the USA. New York was an early epicenter of the US pandemic, highlighting preexisting problems in clinical research and allowing us to assess lessons learned and to identify best practices for the future. Risks and opportunities were categorized broadly into three areas, protecting the welfare and safety of human subjects, ensuring trust in science and medicine, and implementing efficient, ethical, and compliant clinical research. Analysis of conference proceedings, and recent publications, shows a need for preparedness that is more effective, robust partnerships, and organizational systems and standards to strengthen the ethical and responsible conduct of research.