Clinical trials that aim to establish efficacy in the target population need to have an adequate control group. Although scientific principles for efficacy evaluation apply universally, actual choices of control in each region seem to be unique, reflecting differences in regional guidelines for clinical evaluation, preferences of the population, and constraints in study environments. Our survey targeted 76 drugs approved in Japan between April 1999 and July 2000 and showed that active-control was adopted in a significant proportion of controlled phase III trials (74%), while trials with placebo-control accounted for only 18% of the total. The placebo-control was also not so common in phase II (23%). Preference for active-control was observed in many therapeutic fields, but in a few categories such as anti-diabetics placebo-control trials seemed to be the norm. We analysed the possible impact of a new international guideline (ICH-E10) that focuses on the intrinsic defects of active control trial. An economic model suggested that the guideline’s introduction could lead to more placebo-control and that the extent of such shift would depend on the increase in cost for active-control trials and possible changes in the requirements for approval. Future patients seem to be major beneficiaries from the new guideline’s introduction, considering the history of Japanese efficacy evaluation.