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This paper addresses analysis and integrated design of observer-based fault detection (FD) for nonlinear systems. To gain a deeper insight into the observer-based FD framework, definitions and existence conditions for nonlinear observer-based FD systems are studied first. Then, a scheme for an integrated design of observer-based FD systems for affine nonlinear systems is proposed. Our work is considerably inspired by the study on input–output stability and stabilization of nonlinear systems. Examples are given at the end of the paper to illustrate the theoretical results.