The learning healthcare system describes a vision of US healthcare that capitalizes on science, information technology, incentives, and care culture to drive improvements in the quality of health care. The inpatient setting, one of the most costly and impactful domains of healthcare, is an ideal setting in which to use data and information technology to foster continuous learning and quality improvement. The rapid digitization of inpatient medicine offers incredible new opportunities to use data from routine care to generate new discovery and thus close the virtuous cycle of learning. We use an object lesson-sepsis care within the 21 hospitals of the Kaiser Permanente Northern California integrated healthcare delivery system-to offer insight into the critical elements necessary for developing a learning hospital system. We then describe how a hospital-wide data-driven approach to inpatient care can facilitate improvements in the quality of hospital care. Journal of Hospital Medicine 2016;11:S11-S17. © 2016 Society of Hospital Medicine.