De Groot is board certified in Internal Medicine and Infectious Disease. She is the volunteer Medical Director and currently practices Internal Medicine at the Clinica Esperanza (Hope Clinic), a free clinic for Rhode Island residents who do not have health insurance. Annie De Groot and Bill Martin (COO/CIO EpiVax) founded EpiVax in 1998 to use bioinformatics to design epitope-driven vaccines and expanded to offer immunogenicity screening services for protein therapeutics. De Groot, Martin and Dr. Leonard Moise discovered regulatory T cell epitopes, called “Tregitopes”, that are shown to activate regulatory T cells and suppress the immune response. De Groot, Martin and Moise also developed the JanusMatrix tool, that identifies regions of "immune camouflage" used by pathogens to escape immune response. Between 1992 and 2008 De Groot also contributed to the Yale HIV in Prison program and Massachusetts Correctional Institution at Framingham, providing medical treatment to inmates, founded the GAIA Vaccine Foundation for improving global AIDS treatment, and founded a free clinic in Rhode Island, Clinica Esperanza. Her current work at the Clinica Esperanza includes the nurse-run CHEER Clinic, a walk in clinic pilot program that serves as an alternative to non-urgent ER visits. Clinica Esperanza (Hope Clinic) is a volunteer-run free clinic for uninsured adults located in the Olneyville neighborhood of Providence, RI. It provides culturally-attuned and sensitive medical care to more than 9,000 patients since its founding in 2007, 80% of whom are native Spanish speakers.