High-quality scientific evidence may be inadequate to support real world decision-making. Assessment of applicability and generalizability of medical scientific evidence is needed for the practitioner. Often, large differences between trial participants and actual end-users of interventions exist. We present the difference between efficacy and effectiveness in connection with trial design and encourage critical evaluation of external validity. Pragmatic design of trials can be considered a preferred choice to limit the prevailing gap between current evidence and practice.