Large hydropower plants (HPPs) are categorized as critically and strategically important infrastructure facilities in industrialized countries. Therefore, the issues of ensuring HPPs safety are of paramount importance. In this chapter, the basic aspects of the safety analysis of HPPs, calculation and experimental substantiation of the strength, and resource and reliability of the main equipment are discussed. The scientific and technical measures to ensure safety of HPPs are presented. As a defining measure of safety, it is proposed to ensure the protection of HPPs from severe accidents and disasters according to risk criteria. The main provisions of the risk assessment are presented on the basis of a sequential analysis of loads, features of stress-strain states, characteristics of mechanical properties, and limit states of hydraulic equipment of HPPs. The issues of calculation and experimental evaluation of hydro turbine's resource, which limit the safety of HPPs, are considered. The features of technical diagnosis of hydraulic turbines are considered; characteristic defects and damages are described. The main provisions of the estimated residual life of hydro turbines are presented. The results of the risk estimates of HPPs and hydro turbine resource are given.