In this work we present a Grid‐based optimization approach performed on a set of parameters that affects both the geometric and grey‐level appearance properties of a three‐dimensional model‐based algorithm for cardiac MRI segmentation. The search for optimal values was assessed by a Monte Carlo procedure using computational Grid technology. A series of segmentation runs were conducted on an evaluation database comprising 30 studies at two phases of the cardiac cycle (60 datasets), using three shape models constructed by different methods. For each of these model‐patient combinations, six parameters were optimized in two steps: those which affect the grey‐level properties of the algorithm first and those relating to the geometrical properties, secondly. Two post‐processing tasks (one for each stage) collected and processed (in total) more than 70000 retrieved result files. Qualitative and quantitative validation of the fitting results indicates that the segmentation performance was greatly improved with the tuning. Based on the experienced benefits with the use of our middleware, and foreseeing the advent of large‐scale tests and applications in cardiovascular imaging, we strongly believe that the use of Grid computing technology in medical image analysis constitutes a real necessity.