We present and analyze the behavior of an evolutionary algorithm designed to estimate the parameters of a complex organ behavior model. The model is adaptable to account for patient's specificities. The aim is to finely tune the model to be accurately adapted to various real patient datasets. It can then be embedded, for example, in high fidelity simulations of the human physiology. We present here an application focused on respiration modeling. The algorithm is automatic and adaptive. A compound fitness function has been designed to take into account for various quantities that have to be minimized. The algorithm efficiency is experimentally analyzed on several real test cases: 1) three patient datasets have been acquired with the “breath hold” protocol, and 2) two datasets corresponds to 4-D CT scans. Its performance is compared with two traditional methods (downhill simplex and conjugate gradient descent): a random search and a basic real-valued genetic algorithm. The results show that our evolutionary scheme provides more significantly stable and accurate results.