Health care-associated infections, a significant source of morbidity and mortality, remain a major patient safety problem even as policy and programmatic efforts designed to reduce preventable health care-associated infections have increased. The broad, long-term objective of our investigation was to discover additional knowledge on infection control practices in health care that would advance this important, legislatively mandated goal in the United States. We undertook in Phase 1 of a two-phased sequential mixed-methods study, a qualitative investigation to describe the phenomena of infection prevention, surveillance, and control in hospitals in the United States, exploring the organizational processes that improve infection control behavior at the bedside and accommodate variations in clinical care settings. In this case study, we focus on the Phase 1 qualitative activities, discussing our study design, sampling plan, and the sequenced steps we followed in our data collection, analysis, and interpretation. We purposively constituted the sample to include a variety of hospital personnel from diverse health care settings to ensure that a range of occupational and organizational perspectives were represented. We conducted in-depth interviews to obtain comprehensive description about the current structure and processes of infection control. The participants' narrative accounts yielded a nuanced understanding of current infection prevention, surveillance, and control in U.S. health care and facilitated our exploration of the meanings and values participants ascribe to their involvement in infection prevention and control, as well as the contextual circumstances that shaped their perceptions and experiences. These data also informed refinements to a quantitative survey that was administered in Phase 2.