In this paper, we investigate the joint effects of nonlinear distortions due to high-power amplifier (HPA) and radio-frequency (RF) crosstalk on the performance of a multiple-input multiple-output-orthogonal frequency division multiplexing (MIMO-OFDM) system. The performance of the vertical bell laboratories layered space-time (VBLAST) MIMO-OFDM system, in terms of bit error rate (BER) and system capacity, is derived and evaluated for a Rayleigh flat fading channel. In the performance analysis, M-ary quadrature amplitude modulation (M-QAM) is considered and the joint effects of nonlinear HPA distortions and RF crosstalk are studied. Theoretical results and comparisons are provided for several system parameters, such as the input back-off (IBO) and crosstalk intensity. It is shown that the results obtained from the theoretical study are very close to the ones obtained from the simulation. Indeed, we introduce a nonlinear distortion cancellation (NDC) technique to estimate and mitigate nonlinear distortions and crosstalk effects jointly.