With a particular focus on the distillation of highly viscous or self-polymerized mixtures, this study reports the hydrodynamic and mass transfer performance of two flow-guided sieve trays, including their pressure drop, entrainment, weeping and tray efficiency, obtained experimentally with an air-water/oxygen system in a Φ600 mm plexiglass column. The results show that the 8 mm hole flow-guided sieve tray tested shows better characteristics than the 7 mm flow-guided hole tray in terms of pressure drop and mass transfer. Then we present practical industrial examples of applications of the flow guided trays for distillation of viscous mixtures, i.e., the separation of vinyl acetate (VAC) from a polyvinyl acetate (PVAC) polymer solution with dynamic viscosity μ=50,000 mPas, the separation of highly unsaturated C5 mixtures by extractive distillation, and the distillation of thick, condensed and highly viscous fermentation mixtures made from fermented mash. It is demonstrated that flow-guided sieve trays with relatively large holes are an excellent candidate for distillation of mixtures with suspended solids, or concentrated/self-polymerized polymer solutions.