This paper proposes a novel subspace approach towards direct identification of a residual model for fault detection and isolation (FDI) in a system with non-uniformly sampled multirate (NUSM) data without any knowledge of the system. From the identified residual model, an optimal primary residual vector (PRV) is generated for fault detection. Furthermore, by transforming the PRV into a set of structured residual vectors, fault isolation is performed. The proposed algorithms have been applied to ail experimental pilot plant with NUSM data for sensor FDI, where different types of faults are successfully detected and isolated, fully validating the practicality and utility of the developed theory. (c) 2006 Elsevier Ltd. All rights reserved.