Results of RWD-based comparative effectiveness or safety studies are now being considered by HTA agencies and other decision-making bodies. Yet there remain concerns about the validity of this type of evidence and questions of when to use it to inform decision-making. The target trial framework has begun to emerge as a preferred approach. Some major recent research efforts such as OPERAND and RCT-DUPLICATE emulated published randomized controlled trials using the target trial framework in an effort to understand when RWD-based studies can produce the same results. This session will include highlights of RCT-DUPLICATE and OPERAND and discussion of important learnings, advantages, and challenges of target trial emulation.