OBJECTIVES The aim of this study is to assess health care expenditure by disease in order to provide detailed analyses of resource allocations for 2012, based on the French health care system database. METHODS Using information about 60 millions of individuals from the general scheme insurance database (85% of the French population), we identified all people who received care for each of 56 groups of diseases or medical events or treatments, which are frequent, severe and/or costly. Algorithms have been applied to each patient, using ICD-10 diagnoses for long-term chronic diseases or hospital stays, specific drugs or medical procedures. Costs of all reimbursed expenditures (outpatient/inpatient care, disability/sickness benefits) were extracted per individual for a top-down method allocated expenditure to each of the 56 diseases based on the average expenditure by disease calculated for individuals with only one disease. All expenditures were thereafter extrapolated to the whole population to fit national health account aggregates. RESULTS Among the 146 billion euros of expenditures (all insurance schemes), 22.1 billion (15%) were related to psychiatric disorders and treatments, 14 (10%) to cancer, 14.6 (10%) to cardiovascular diseases, 7.5 (5%) to diabetes, 6.6 (5%) to vascular-risk treatments, 6.1 (4%) to neurologic disorders, 3.5 (2%) to chronic respiratory diseases, 4.7 (3%) to inflammatory/rare diseases/HIV, 3.5 (2%) to treated chronic renal insufficiency, 1.4 (1%) to liver/pancreas diseases, 1.5 (1%) to chronic pain killer users and 4 (3%)  to other long-term chronic diseases. Isolated hospitalizations represented 32.8 billion € (23%), basic care 14.6 (10%) and maternity 9.1 (6%). This analysis also provides detailed patterns of expenditures by diseases. CONCLUSIONS Our study provides helpful information to policy makers by monitoring the performance of the health care system at a disease-based level. This tool will be used to forecast the impact of ageing and epidemiologic patterns on health expenditures.