This report describes the principal methods used in the development, conduct, and analysis of the research study “Health Assessment of Persian Gulf War Veterans from Iowa” (Iowa Gulf War Study). The methods presented include an outline of the organizational structure, study timeline, hypotheses, outcome definitions, and study design. Adhering to a strict timeline, the study protocol and instruments were developed, and a stratified sample of 3,695 military personnel (76% participation) was located and surveyed by structured telephone interview. The study tracked personnel from all service branches residing nationally and internationally, including those discharged from service. This study required development and implementation of methods appropriate to analysis of data collected in a complex sampling framework and methodological procedures to ensure scientific rigor in a highly public and politicized environment. Statistical analyses were conducted on a priori health outcomes and required development of methods to compute Cochran-Mantel-Haenszel adjusted rate differences. This environment facilitated rapid implementation, critique by scientific and public advisors, a high participation rate, and rapid publication.