Adsorption of hexane isomers in high silica MFI and MEL zeolites was studied by means of quasi-equilibrated temperature-programmed desorption and adsorption and Monte Carlo simulations. Configurational bias and continuous fractional component Monte Carlo were applied for these systems, and their efficiency and effectiveness were compared. All branched hexane isomers, i.e., 2-methylpentane, 3-methylpentane, 2,3-dimethylbutane, and 2,2-dimethylbutane, were used. The agreement between experimental and calculated adsorption isobars confirmed that quasi-equilibrated temperature-programmed desorption and adsorption is an effective method for studying adsorption of branched alkanes in zeolites. Detailed literature review on adsorption of branched paraffins in MFI revealed diffusion limitations which make reaching adsorption equilibria of these molecules difficult with isothermal approach at low temperatures. Temperature-dependent measurements conducted in this work largely allowed avoiding such limitations. Adsorption equilibria of branched alkanes in MEL zeolite have been studied experimentally for the first time. Detailed analysis of the adsorption behavior of these systems revealed the presence of two adsorption sites located in the different intersections of the straight channels characteristic of the MEL framework. Molecular simulations for adsorption of mixtures of branched hexane isomers showed potential application of the MFI and MEL zeolites in separation of mono- and dibranched isomers.