Activated layered double hydroxides (LDHs) with high crystallinity, obtained by calcination/rehydration of LDH precursors synthesized by urea decomposition, have higher catalytic activity in acetone self-condensation and Knoevenagel reactions than less crystalline materials obtained from LDH precursors synthesized by titration co-precipitation. The activated LDHs possess both basic and acidic sites. High resolution transmission electron microscopy (HRTEM) confirms that the highly crystalline activated LDHs retain the lattice structure of the LDH precursors with lattice parameters a = b = 0.31 +/- 0.01 nm and alpha = 60 +/- 2 degrees. An acid-base catalytic mechanism has been proposed to interpret the catalytic behavior based on the fact that acid-base hydroxyl group pairs on the activated LDH surface have a separation of 0.31 nm. It is proposed that the active sites are mainly located on the ordered array of hydroxyl sites on the basal surfaces rather than on the edges, as has been previously suggested. (c) 2007 American Institute of Chemical Engineers.