His work at the intersection of population and individual health has had a unique, sustained influence on the developing field of biomedical informatics. He was a pioneer of real time biosurveillance, tracking infections and detecting outbreaks with diverse data. He has long advocated for patient participation in producing and accessing data and was a pioneer of the first personal health systems, using crowdsourced knowledge from online patient networks, and advancing participatory medicine and engagement in clinical trials.
Cognizant of the limitations of extant electronic health record systems, Mandl developed a widely-adopted, highly influential approach (SMART)--substitutable apps that run universally on health IT systems. SMART lets innovators reach market scale and patients and doctors access an “app store for health.” Through the 21st Century Cures Act, SMART is now regulated as the standard interface by which patients, providers, and apps access data from electronic health records. He applies open source inventions to lead EHR research networks.