A probabilistic fracture mechanics model was developed to analyse the failure probability of a typical high power density reactor pressure vessel. The major causes for the nuclear reactor pressure vessel failure include fatigue, corrosion fatigue and brittle failure. All these causes are greatly affected by the stress loading conditions, material properties (aged by neutron damage), and defects embedded in the structure. Both an analytical first-order second-moment approximation and a hybrid methodology were employed in this study. In addition to the static scatter of the pre-existing cracks and material properties, a random walk model based on the operating history was introduced to represent the random occurrence of the abnormal transient stresses. The failure mode is defined as the brittle failure caused by a critical crack, meaning the stress intensity factor around a critical crack exceeding the fracture toughness of the pressure vessel material. Through a sample study on a typical high power density nuclear power plant, it was found that the vessel failure probability is about 4 × 10 −4 at the 40th year of operation and the failure rate is in the order of 5 × 10 −6 per vessel per year, which had reasonable agreement with the value of 10 −4−10 −6 as reported based on real-world statistics. In addition to the failure probability caused by fatigue crack growth, the reliability of a Low Temperature Overpressure incident was also evaluated.