Randomized controlled trials (RCTs) have been considered the reference standard for evaluation of drug effects. Controversy exists concerning observational studies because of the lack of blinding and the risk of uncontrolled confounding. However, RCTs also have limitations, including short follow-up and relatively small study populations, which make it impossible to examine rare events and cross-over problems. None of the designs provides perfect information and both designs are needed in the evaluation of drug effects.