High-purity distillation columns present challenges of nonlinearity, interactions, directionality, and ill-conditioning for the control systems and thus exhibit poor controller performance. Effects of these issues on the performance of model predictive control in operations in near-azeotropic regions are investigated. A dynamic model of a pilot-scale distillation column is simulated and controlled by a linear model predictive controller. As the system moves towards the azeotropic region, the nonlinearity, directionality, and interactions of the system increase. A significant decline is observed in the system control performance since the controller incurs overshoots and offsets for negative and positive setpoint changes. The integral time absolute errors are substantially higher near the azeotropic region. Only a small operating range is able to ensure sufficient controllability near the azeotropic region.