The article stems from the ongoing legislative debate occurring in Italy in order to detect and rationalise the essential constitutional prerequisites and indicators which a statutory law providing for mandatory vaccinations should comply with. The main goal is to propose a set of conditions which can reasonably guarantee the constitutional compatibility of mandatory vaccination with the general principles and individuals' rights involved. The analysis is conducted by implementing the comparative methods: the constitutional case-law of those national legal orders in which forms of mandatory vaccinations are established has been selected and examined, with the aim to provide legislators with a «constitutional map» in this context. The comparative survey clearly shows that elements such as the scientific grounds for legislative choices or the existence of clauses of flexibility (linked with the health condition of individuals) may convert mandatory vaccinations as legitimate, even if non mandatory, tool for the protection of individual and public health.