The United States (US) Department of Veterans Affairs (VA) Mid-Atlantic Mental Illness Research, Education, and Clinical Center (MIRECC) Post-Deployment Mental Health (PDMH) multi-site study examines post-deployment mental health in US military Afghanistan/Iraq-era veterans. The study includes the comprehensive behavioral health characterization of over 3600 study participants and the genetic, metabolomic, neurocognitive, and neuroimaging data for many of the participants. The study design also incorporates an infrastructure for a data repository to re-contact participants for follow-up studies. The overwhelming majority (94%) of participants consented to be re-contacted for future studies, and our recently completed feasibility study indicates that 73-83% of these participants could be reached successfully for enrollment into longitudinal follow-up investigations. Longitudinal concurrent cohort follow-up studies will be conducted (5-10+ years post-baseline) to examine predictors of illness chronicity, resilience, recovery, functional outcome, and other variables, and will include neuroimaging, genetic/epigenetic, serum biomarker, and neurocognitive studies, among others. To date, the PDMH study has generated more than 35 publications from the baseline data and the repository has been leveraged in over 20 publications from follow-up studies drawing from this cohort. Limitations that may affect data collection for a longitudinal follow-up study are also presented.