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Many existing works on space-time block codes (STBC) assume the channels are block-wise constant, but this assumption does not always hold. In the more general case of time-selective channels, the channel matrix is no longer orthogonal, so inter-symbol interference (ESI) is generated and the performance is greatly reduced. Several decoders have been proposed to eliminate the ESI, but it remains unclear how and to what extent the performance is affected by the ISI. In this paper, we introduce an approach to analyze the performance of STBC over time-selective channels, with arbitrary numbers of antennas for which orthogonal STBC's are defined. Exact error performances are obtained in closed form. Furthermore, the analysis reveals the relationship between the ISI and the structure of STBC matrices. Considering G i systems, we then propose one proposition and two design criteria, following which it is easy to design or search for better STBC's that have less ISI compared with the original code matrix.