Background The study objectives were to describe the incidence and the nature of patient safety incidents (PSIs) in primary care general practice settings, and to explore the association between these incidents and practice or organizational characteristics. Methods GPs, randomly selected from a national influenza surveillance network (n = 800) across France, prospectively reported any incidents observed each day over a one-week period between May and July 2013. An incident was an event or circumstance that could have resulted, or did result, in harm to a patient, which the GP would not wish to recur. Primary outcome was the incidence of PSIs which was determined by counting reports per total number of patient encounters. Reports were categorized using existing taxonomies. The association with practice and organizational characteristics was calculated using a negative binomial regression model. Results 127 GPs (participation rate 79%) reported 317 incidents of which 270 were deemed to be a posteriori judged preventable, among 12,348 encounters. 77% had no consequences for the patient. The incidence of reported PSIs was 26 per 1000 patient encounters per week (95% CI [23‰ -28‰]). Incidents were three times more frequently related to the organization of healthcare than to knowledge and skills of health professionals, and especially to the workflow in the GPs' offices and to the communication between providers and with patients. Among GP characteristics, three were related with an increased incidence in the final multivariable model: length of consultation higher than 15 minutes, method of receiving radiological results (by fax compared to paper or email), and being in a multidisciplinary clinic compared with sole practitioners. Conclusions Patient safety incidents (PSIs) occurred in mean once every two days in the sampled GPs and 2% of them were associated with a definite possibility for harm. Studying the association between organizational features of general practices and PSIs remains a major challenge and one of the most important issues for safety in primary care.