BACKGROUND: Routine family history risk assessment for chronic diseases could enable primary care practitioners to efficiently identify at-risk patients and promote preventive management strategies. OBJECTIVES: To investigate patients' understanding and responses to family history risk assessment in primary care. METHOD: A mixed methods study set in 10 Eastern England general practices. Participants in a family history questionnaire validation study were triaged into population or increased risk for four chronic diseases (type 2 diabetes, cardiovascular disease, breast cancer, colorectal cancer). Questionnaires completed immediately prior to the family history consultation (baseline) and 4 weeks later (follow-up) assessed the psychological impact, including State-Trait Anxiety Inventory scores. Semi-structured interviews explored the meaning participants gave to their personal familial disease risk. RESULTS: Four hundred and fifty-three participants completed both baseline and follow-up questionnaires and 30 were interviewed. At follow-up, there was no increase in anxiety among either group, or differences between the groups [difference in mean change 0.02, 95% confidence interval -2.04, 2.08, P = 0.98]. There were no significant changes over time in self-rated health in either group. At follow-up, participants at increased risk (n = 153) were more likely to have recent changes to behaviour and they had stronger intentions to make changes to diet (P = 0.001), physical activity (P = 0.006) and to seek further information in the future than those at population risk (n = 300; P < 0.001). Using qualitative analysis, five themes were developed representing ways in which participants gave meaning to familial disease risk ('Being reassured', 'Controlling risk', 'Dealing with it later', 'Beyond my control', 'Disbelieving the risk'). The meanings they attributed to increased risk appeared to shape their intention to undertake behaviour change. CONCLUSION: Routine assessment for familial risk of chronic diseases may be undertaken in primary care without causing anxiety or reducing self-rated health. Patient responses to family history risk assessment may inform promotion of preventive management strategies.