Quantum mechanical plus molecular mechanical direct chemical dynamics were used, with electrospray tandem mass spectrometry experiments, potential energy surface calculations, and RRKM analyses, to study the gasphase collision-induced dissociation (CID) of protonated urea. The direct dynamics were able to reproduce some of the experimental observations, in particular the presence of two fragmentation pathways, and, thus, to explain the dynamical origin of the two fragmentation ions observed in the CID spectra. A shattering dissociation mechanism takes place during the collision, and it becomes more important as the collision energy increases, thus explaining the linear increase of the high-energy reaction path (loss of ammonia) versus collision energy. By combining the different theoretical and experimental findings, a complete dynamical picture leading to the fragmentation was identified: (i) Oxygen-protonated urea, the most stable structure in the gas phase, must first isomerize to the nitrogen-protonated form. This can happen by multiple CID collisions or in the electrospray ionization process, (ii) Once the nitrogen-protonated isomer is formed, it can dissociate via two mechanisms: i.e, a slow, almost statistical, process forming a NH4--NHCO intermediate that rapidly dissociates or a fast nonstatistical process which may lead to the high-energy products.