OBJECTIVES: Some observational studies fail to gain momentum while others move smoothly to successful completion. This study set out to determine which factors drive physician motivation in prospective observational studies. METHODS: A web based survey was designed using input from structured literature review, investigators and experienced observational study researchers.  It comprised 35 questions covering: Scientific and clinical factors (7), Study requirements (11), Operational considerations (6), Financial and legal considerations (4), Personal and professional factors (7). Respondents were asked to rate factors on a scale -5 to +5 (+5 represented very motivational and -5 very de-motivational). Free form comments were also invited. The survey was e-mailed to investigators (n=1160) identified from Citeline® as having performed both prospective observational studies and clinical trials in the last 5 years.   RESULTS: Overall response was 15% (n=174), Europe (55%) and North America (45%) covering Community care (34%), University hospitals (29%), General hospitals (24%) and dedicated research facilities (13%). Most respondents had experience of >5 clinical trials in the last 5 years (81%) but fewer had similar experience with observational studies (40%). Responses indicate that not all physicians are equally motivated by the same factors. However most important motivational factors were in the scientific and clinical, financial and legal domains including studies which advance medical knowledge and / or patient management and acceptable honoraria.  Less important factors were in the personal and professional domain including opportunities to speak at conferences or publish the data.  Investigators more experienced in observational research placed greater motivational value on advancing medical knowledge and/ or patient management than less experienced colleagues. CONCLUSIONS: The findings provide good insight into which factors really motivate physicians and more customised motivational approaches are likely to minimise study risks. Further sub analyses of the survey data may identify more detailed strategies to pursue.