In order to understand how additives influence the structure and electrical properties of active layers in thin-film devices, a compositionally identical but structurally different guest-host system based on the syn and anti isomers of triethylsilylethynyl anthradithiophene (TES ADT) is systematically explored. The mobility of organic thin-film transistors (OTFTs) comprising anti TES ADT drops with the addition of only 0.01% of the syn isomer and is pinned at the mobility of OTFTs having pure syn isomer after the addition of only 10% of the isomer. As the syn isomer fraction increases, intermolecular repulsion increases, resulting in a decrease in the unit-cell density and concomitant disordering of the charge-transport pathway. This molecular disorder leads to an increase in charge trapping, causing the mobility of OTFTs to drop with increasing syn-isomer concentration. Since charge transport is sensitive to even minute fractions of molecular disorder, this work emphasizes the importance of prioritizing structural compatibility when choosing material pairs for guest-host systems.