A balance control method, the proportional-integral sliding mode control (PISMC), is proposed to control the tilt attitude of an experimental two-wheel vehicle system (TWVS). Based on our previous work of implementing a generalized PISMC to control a linearized dynamical system, this paper extends the algorithm to a wider range: First, the control design of a weighted-control system is proposed. Secondly, our algorithm was realized and verified in a TWVS using its original nonlinear model. Thirdly, a systematical way to tune parameters are presented. The robustness of the proposed algorithm is also discussed in this paper. The simulation results of this work validate that the PISMC has better robustness to counteract the external disturbances than the conventional sliding mode control (SMC) does. Additionally, the experimental results show that the PISMC is capable of autonomously balancing the TWVS more effectively than the conventional SMC. The successful implementation of our algorithm potentially extends the implementation of the PISMC to various nonlinear and emerging systems.