Dr. Hennessy conducts research in the field of pharmacoepidemiology, which is the study of the health effects of drugs and other medical products in populations. His team identified a survival benefit of potassium supplementation in users of loop diuretics, and studied serious health consequences of drug-drug interactions involving high-risk drugs including anticoagulants, antidiabetic agents and antiplatelet agents. His research has produced crucial knowledge about the cardiovascular safety of many widely-used drugs for mental health conditions in including ADHD, depression, and schizophrenia. He also evaluated an early approach to using medical insurance data to improve prescribing, finding it ineffective despite its federal mandate. This contributed to the omission of a requirement for drug utilization review programs in Medicare Part D. He co-led a pair of studies demonstrating the effectiveness and safety of the SA14-14-2 vaccine for Japanese encephalitis (JE), which subsequently led to the immunization of millions of children per year in populous countries including Cambodia, India, Malaysia, Nepal, Sri Lanka, and Thailand. Use of that vaccine has been credited with reducing the incidence of JE. He co-developed the trend-in-trend research design for studying the effects of rapidly increasing or declining exposures. He was the senior author of one of two citizen petitions to the US Food and Drug Administration that led to re-labeling of metformin, the best-proven oral drug for diabetes, to permit its use in persons with mild to moderate renal insufficiency. Dr. Hennessy is a past scientific chair and past president of the International Society for Pharmacoepidemiology, and has served on FDA’s Drug Safety and Risk Management Advisory Committee. He is an elected member of the National Academy of Medicine.