Abstract We describe the 3-iodopropyl acetal moiety as a simple cleavable unit that undergoes acid catalyzed hydrolysis to liberate HI (pKa ~ -10) and acrolein stoichiometrically. Integrating this unit into linear and network polymers gives a class of macromolecules that undergo a new mechanism of degradation with an acid amplified, sigmoidal rate. This trigger-responsive self-amplified degradable polymer undergoes accelerated rate of degradation and agent release.