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In this paper, a two stage hybrid interference cancellation and equalization framework is proposed for interference cancellation in the uplink of multiple-input multiple-output orthogonal frequency division multiplexing (MIMO-OFDM) systems. The first stage uses time domain equalization to suppress cochannel interference, mitigate asynchronism, and shorten the postequalization channel response to be no longer than the length of the cyclic prefix. The second stage performs low-complexity single tap equalization and detection in the frequency domain. The framework is developed specifically for spatial multiplexing and is applied to multiuser MIMO-OFDM systems with asynchronism between users as well as to single-user MIMO-OFDM systems. Various equalizer design methods are proposed that determine the coefficients directly from the training data and are compared with methods based on channel estimates. The equalizer coefficients and postequalization channel response are found by solving a joint optimization that maximizes the signal to interference-plus-noise ratio (SINR) in the frequency domain. Simulations compare various training-based methods and show the proposed methods provide good bit error rate (BER) and SINR performance in a variety of interference scenarios.