Only three cofactor-free decarboxylases have been characterized so far. Their capacity to stabilize the evolving carbanion in the transition state without the delocalization into a cofactorsystem has spurred significant interest in their mechanisms. While arylmalonate decarboxylase has been thought to be selective for pro-R decarboxylation, our results for the AMDase ICPLLG variant show that inverse substrate binding and loss of pro-S carboxylate is possible. Moreover, alkenyl malonates are exclusively converted with inversion of the configuration at the stereogenic center, whereas (S)-selective AMDase variants having C188 decarboxylate aromatic malonates with retention.