Abstract Background Clinical research is mostly conducted among hospitalized patients, which restricts the generalizability of research results. The involvement of GPs in research has been consistently highlighted as a factor associated with successful study recruitment. Objectives To assess GPs’ motivations and willingness to participate in primary care research as investigators and to identify factors associated with their willingness. Methods We conducted an observational, cross-sectional study in Normandy, France, with a self-questionnaire sent to 3002 GPs. We collected data on GPs’ socio-demographic characteristics, their experiences and their expectations regarding research, and their reasons for non-participation. Results Overall, 489 questionnaires were collected. Two hundred and forty-six GPs (50.3%) were interested in participating in clinical research as investigators. The two main conditions for participation as investigators were the relevance of the study topic for clinical practice (80.5%) and the feedback of study results (80.1%). The two main reasons for non-participation were lack of time (79.4%) and administrative burden (43.6%). Age between 27 and 34 years (adjusted odds ratio [AOR] = 2.86, P = 0.004) and GP trainer status (AOR = 2.41, P < 0.001) were associated with willingness to participate in primary care research. Age between 60 and 70 years (AOR = 0.53, P = 0.03) and locum status (AOR = 0.40, P = 0.04) were associated with non-participation in research. Conclusions Based on our results, we were able to establish a profile of GPs willing to participate in primary care research as investigators. GPs’ involvement should be based on their preferred areas of research. Different incentives such as a dedicated clinical research nurse or financial support could also be considered.