There is a pressing need for practical clinical trials (PCTs) that are more relevant to clinicians and decision-makers, but many are unaware of these trials. Furthermore, such trials can be challenging to conduct and to report. The objective of this study was to build on the seminal paper by Tunis et al (Practical clinical trials. Increasing the value of clinical research for decision making in clinical and health policy. JAMA. 2003;290:1624-1632.) and to provide recommendations and examples of how practical clinical trials can be conducted and the results reported to enhance external validity without sacrificing internal validity. We discuss evaluating practical intervention options, alternative research designs, representativeness of samples participating at both the patient and the setting/clinician level, and the need for multiple outcomes to address clinical and policy implications. We provide a set of specific recommendations for issues to be reported in PCTs to increase their relevance to clinicians and policymakers, and to help reduce the gap between research and practice.