Abstract The design and realization of Adaptive Neuro-Fuzzy Inference System (ANFIS) controller based on Field Programmable Gate Array (FPGA) is presented in this paper. The controller intended to control the temperature of medical oven. A novel design of digital ANFIS is presented here for the implementation process. Different controllers are designed and their results are compared using MATLAB program to show the ANFIS superiority. The designed controllers tested for cell cultures application at 37.5. A reduction is made for the designed digital ANFIS due to the used FPGA limitations. The reduced design minimizes the utilized slices from 366% to 3% and LUTs from 364% to 3%. The reduced design reached an optimum size for this controller to utilize a smallest memory size. A real-time FPGA implementation of the proposed digital ANFIS have been done and verified through Xilinx ISE 14.6 using the VHDL language. The VHDL code for the controller is produced, aggregated and downloaded on the FPGA Spartan 3A/AN FPGA kit. A comparison between the simulation and implementation results is made. The matching between these results proves the effectiveness and robustness of the proposed digital ANFIS and the excellent performance of the FPGA based controller.