Weak acids are known to enhance the activity of amines in aldol condensation reactions on silica-based catalysts. The effects of acid strength and arrangement of the promoting site with respect to a secondary amine have been investigated in the aldol condensation of 4-nitrobenzaldehyde with acetone. Changing the substituent of this secondary amine from a methyl to an ethyl group decreases the activity. An intra-molecular OH function provided by a primary alcohol incorporated on the b-carbon of the amine sub-stituent exhibits a similar cooperativity as an intermolecular OH function provided by neighboring surface silanols. A maximum activity was achieved when the secondary amine with the same primary alcohol-containing substituent was surrounded by surface silanols, indicating the potential advantage of simultaneously activating both reactants by the formation of a hydrogen bond in contrast to the consecutive activation when there is only one promoting site in the vicinity of the amine. Changing the alcohol to stronger acids resulted in a reduced cooperativity with increasing acid strength. After removing the silanols from the surface, the activity of the catalysts which exhibit an intramolecular cooperativity retained about 68–83% of their activities while the activity of the conventional secondary amine was reduced by a factor of four compared to its intermolecularly cooperative counterpart.