Hydrotalcites (HTs) of different, well-defined platelet sizes were hydrothermally synthesized. Activation via calcination and rehydration resulted in highly active catalysts. Their activities in the self-condensation of acetone at 273 K showed a linear increase with the amount of accessible Bronsted basic sites as determined by CO2 adsorption. The number of accessible sites, based on the CO2/Al ratio, was below 5%. Both results support our model in which only basic sites near edges of HT platelets are partaking in aldol condensations. Besides incorporation of interlayer OH- upon rehydration, the hexagonal morphology changed as a result of activation into a more irregular but still layered structure containing mesopores (< 10 nm). In contrast to this, HTs with interlayer OH- prepared via ion exchange preserved their original hexagonal structure, but they lacked the high catalytic activity. The results show an enhanced activity of interlayer OH- close to disordered edges, obtained via rehydration, in contrast to interlayer OH-in a regular HT structure.