It is difficult to enlist the participation of medical general practitioners (GPs) in research studies. We aimed to determine the willingness of GPs in central Switzerland to participate in research, and to identify factors that facilitate or hinder research participation by GPs. To that end, we conducted a postal questionnaire survey of all 268 active GPs in the canton of Lucerne. The survey explored their interest in participating in research projects (yes/no) and factors that potentially influence their participation (5-point Likert scale from "very important" to "not at all important"). We contacted all non-responders by phone. Background information of the GPs was retrieved from the database of the cantonal association of physicians. Associations between willingness to participate in research and GP's age, gender, type and location of practice, and the perceived relevance of facilitators were investigated via multiple logistic regression. Out of 268 GPs, 115 (43%) agreed to be contacted for future research projects. Willingness was associated with age (willing: 55% ≤ 40 y vs. 33% > 60 y) and gender (44% male vs. 38% female), and to some degree with the type of practice (50% group vs. 31% single), and location (46% urban vs. 38% rural), independently from each other. Scientists should develop methods to motivate and support GPs in single and rural practices to participate so research is representative of primary care as a whole.