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New methods for predicting the worst-case crosstalk caused by intersymbol interference and the worst-case eye opening including crosstalk effect are proposed. The new method for predicting the worst-case crosstalk is based on simulated or measured crosstalk caused by a single bit aggressor signal. By using the derived worst-case crosstalk and the no-crosstalk worst-case eye opening, we can get worst-case eye opening including crosstalk effect. The proposed methods are exactly valid for packaging component and system with linear I/O devices as the signal source and load. They can also be extended to some nonlinear I/O cases with approximations.