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This paper proposes an advanced robust multivariable control strategy for a powered wheelchair system. The new control strategy is based on a combination of the systematic triangularization technique and the robust neuro-sliding mode control approach. This strategy effectively copes with parameter uncertainties and external disturbances in real-time in order to achieve robustness and optimal performance of a multivariable system. This novel strategy reduces coupling effects on a multivariable system, eliminates chattering phenomena, and avoids the plant Jacobian calculation problem. Furthermore, the strategy can also achieve fast and global convergence using less computation. The effectiveness of the new multivariable control strategy is verified in real-time implementation on a powered wheelchair system. The obtained results confirm that robustness and desired performance of the overall system are guaranteed, even under parameter uncertainty and external disturbance effects.