Objectives Cancer survival and stage of disease at diagnosis and treatment vary widely across Europe. These differences may be partly due to variations in access to investigations and specialists. However, evidence to explain how different national health systems influence primary care practitioners’ (PCPs’) referral decisions is lacking. This study analyses health system factors potentially influencing PCPs’ referral decision-making when consulting with patients who may have cancer, and how these vary between European countries. Design Based on a content-validity consensus, a list of 45 items relating to a PCP’s decisions to refer patients with potential cancer symptoms for further investigation was reduced to 20 items. An online questionnaire with the 20 items was answered by PCPs on a five- point Likert scale, indicating how much each item affected their own decision-making in patients that could have cancer. An exploratory factor analysis identified the factors underlying PCPs’ referral decision-making. Setting A primary care study ; 25 participating centres in 20 European countries. Participants 1830 PCPs completed the survey. The median response rate for participating centres was 20.7%. Outcome measures The factors derived from items related to PCPs’ referral decision-making. Mean factor scores were produced for each country, allowing comparisons. Results Factor analysis identified five underlying factors: PCPs’ ability to refer ; degree of direct patient access to secondary care ; PCPs’ perceptions of being under pressure ; expectations of PCPs’ role ; and extent to which PCPs believe that quality comes before cost in their health systems. These accounted for 47.4% of the observed variance between individual responses. Conclusions Five healthcare system factors influencing PCPs’ referral decision-making in 20 European countries were identified. The factors varied considerably between European countries. Knowledge of these factors could assist development of health service policies to produce better cancer outcomes, and inform future research to compare n