Decision makers in health care are increasingly interested in using high-quality scientific evidence to support clinical and health policy choices; however, the quality of available scientific evidence is often found to be inadequate. Reliable evidence is essential to improve health care quality and to support efficient use of limited resources. The widespread gaps in evidence-based knowledge suggest that systematic flaws exist in the production of scientific evidence, in part because there is no consistent effort to conduct clinical trials designed to meet the needs of decision makers. Clinical trials for which the hypothesis and study design are developed specifically to answer the questions faced by decision makers are called pragmatic or practical clinical trials (PCTs). The characteristic features of PCTs are that they (1) select clinically relevant alternative interventions to compare, (2) include a diverse population of study participants, (3) recruit participants from heterogeneous practice settings, and (4) collect data on a broad range of health outcomes. The supply of PCTs is limited primarily because the major funders of clinical research, the National Institutes of Health and the medical products industry, do not focus on supporting such trials. Increasing the supply of PCTs will depend on the development of a mechanism to establish priorities for these studies, significant expansion of an infrastructure to conduct clinical research within the health care delivery system, more reliance on high-quality evidence by health care decision makers, and a substantial increase in public and private funding for these studies. For these changes to occur, clinical and health policy decision makers will need to become more involved in all aspects of clinical research, including priority setting, infrastructure development, and funding.