AIMS To understand public and general practitioner (GP) opinion on the acceptability of randomized policy design (RPD) studies (cluster randomized trials) of prescription medicines in Scotland. METHODS We surveyed public opinion on the concept of RPD studies in a sample of 1040 adults to determine acceptability and understand how people feel when changes are made to their medicines. We also surveyed GPs (n=1034) about the concept of RPD studies as a tool for improving understanding of comparative effectiveness and safety of medicines in the 'usual care' setting. RESULTS Thirty per cent of people would be happy to receive a letter about randomized policy changes to their therapy, 31% would not mind or had no opinion and 39% would be unhappy. This view was sensitive to the reason for change; effectiveness and safety reasons were most acceptable (96%) and cost saving least acceptable (39%). Only 19% thought randomized policy change was not an acceptable method of determining the best treatments. Eighty-one per cent of respondents were willing for their medical data to be followed up to compare drug treatments (further 10% undecided). Participants reporting long-term medical conditions and those reporting previous changes to drug therapy were more in favour of RPD studies than other participants. Thirty-three per cent (n=341) of GPs responded to our survey. Of these, 45% were in favour of RPD studies, 19% were undecided and 36% not in favour. CONCLUSIONS The public in Scotland is broadly supportive of the concept of randomized policy design studies of medicines, while there is a spread of opinion among GPs.