ISSUE:: Pragmatic trials are designed to reflect real-world product use more accurately than highly controlled explanatory trials. Unfortunately, real world applicability also brings methodological challenges resulting in threats to valid inference. Consequently, pragmatic trials are often not appropriate for regulatory submission. However, information regarding the real-world product can provide useful information for payors, patients and providers. This issue panel will outline several pros and cons of pragmatic trials and discuss innovative (and likely controversial) methodological approaches to address their shortcomings. Advocates for the use of pragmatic clinical trials argue that they provide more generalizable and decision-relevant results than explanatory trials. There has been an increase in publications of studies that are termed ‘pragmatic’ in recent years. This issue panel will discuss the appropriate uses of different study designs, depending upon the endpoint/hypothesis tested. OVERVIEW:: Advocates for the use of pragmatic clinical trials argue that they provide more generalizable and decision-relevant results than explanatory trials. There has been an increase in publications of studies that are termed ‘pragmatic’ in recent years. This issue panel will discuss the appropriate uses of different study designs, depending upon the endpoint/hypothesis tested. Presented by the ISPOR Statistical Methods in HEOR Special Interest Group