The assessment of vaccination coverage at the regional level needs to be improved. The feasibility of routinely estimating vaccination coverage at 24 months of age in the Midi-Pyrénées region was evaluated using the Erasme regional database of the general health insurance system. Reimbursements for mandatory and recommended vaccines among children born in 2004 were compared with results from two other available sources: 24-month health certificates and the General Practitioner Sample (EGB) of the National Health Insurance system. Compared to data from 24-month health certificates used as a reference, vaccination coverage analyzed using the Erasme database significantly underestimates vaccination coverage among children, even after adjusting these data based on the assumption that primary vaccination was administered in free vaccination clinics during the first year of life. The results are close to the regional estimates derived from the EGB. The Erasme database—which is individual-level, free, immediately available, and not subject to reporting biases—can provide information on adherence to vaccination schedules. However, its use likely leads to an underestimation of vaccination coverage, particularly due to the specific bias resulting from changes in children’s health insurance affiliation over the study period. Other biases inherent in the Health Insurance databases—notably the exclusion of vaccinations administered in free vaccination services and the lack of representativeness of all insurance plans—could be addressed in the future, opening up interesting prospects. (R.A.)