Abstract Vapor phase Prins condensation of isobutene with formaldehyde has been studied over boron (BP), aluminum (AlP), titanium (TiP), zirconium (ZrP) and niobium (NbP) phosphates. The catalysts were characterized by elemental analysis, X-ray diffraction, low-temperature adsorption of nitrogen, TPD of ammonia and FTIR of adsorbed pyridine. The conversion of isobutene and formaldehyde over phosphates was found to increase in the following order: BP≪AlP<TiP<ZrP<NbP, while the selectivity to isoprene showed the reverse tendency. The main side reaction was formaldehyde decomposition into carbon monoxide and dihydrogen. It is proposed that isoprene is formed on the Brønsted acid sites of the catalyst, while Mδ+Oδ− ion pairs are responsible for competitive carbon monoxide formation. The high resistance of ZrP and NbP catalysts to deactivation is accounted for by the in situ restoration of the Brønsted acid sites in the presence of water directly during the time course of the reaction.