Public health research requires sound design and thoughtful consideration of potential biases that may influence the validity of results. It also requires careful implementation of protocols and procedures that are likely to translate from the research environment to actual clinical practice. This article is the product of a breakout session from the 2009 Academic Emergency Medicine consensus conference entitled “Public Health in the ED: Screening, Surveillance, and Intervention” and serves to describe in detail aspects of performing emergency department (ED)-based public health research, while serving as a resource for current and future researchers. In doing so, the authors describe methodologic features of study design, participant selection and retention, and measurements and analyses pertinent to public health research. In addition, a number of recommendations related to research methods and future investigations related to public health work in the ED are provided. Public health investigators are poised to make substantial contributions to this important area of research, but this will only be accomplished by employing sound research methodology in the context of rigorous program evaluation.