Apart from their desired effect of reducing the ejection force and punch adhesion, lubricants also have a considerable influence on the tablet hardness, disintegration, and dissolution times due to their inherent hydrophobicity. This study aimed to investigate the influence of the lubricant molecular structure on the aforementioned characteristics. For this purpose, active pharmaceutical ingredients (APIs) with high and low water solubility have been evaluated in combination with 4 different, stearyl-based lubricants. The study showed that the molecular structure of the lubricant had a significant influence on all of the above mentioned tablet characteristics. A good molecular balance between hydrophobic and slightly hydrophilic moieties – as obtained for sodium stearyl fumarate (PRUV®) – resulted in the best overall outcome.