Herein, we report that ASA afforded remarkable activity and selectivity for mesitylene from acetone under continuous conditions not only in liquid but also in supercritical phase. The ASA catalysts were beneficial due to their combination of larger mesopores and moderate overall acid site density of medium strength with a lower number of strong Brønsted acid sites. The optimization of reaction conditions and long-term catalyst stability are examined for maximum mesitylene space-time-yield on ASA. Assessment of the acidity-activity-relationship for this material class is performed based on the degree of silica-doping.