This chapter describes the utilization of computational fluid dynamics (CFD) with neural network (NN) for analysis of medical devices. First, the concept of mathematical modeling and its use for solving engineering problems is presented followed by an introduction to CFD with a brief summary of the numerical techniques currently available. A brief introduction to the standard optimization strategies for NN and the various methodologies in use are also presented. A case study of the design and optimization of scaffolds for tissue engineering heart valve using the combined CFD and NN approach is presented and discussed. This chapter concludes with a discussion of the advantages and disadvantages of the combined NN and CFD techniques and their future potential prospective.