Mechanical response of fuel cladding with local hydride accumulations is crucial in the assessment of cladding integrity at high burn-ups. We have performed high-temperature low-strain rate burst tests on irradiated cladding samples with and without hydride lenses or blisters to seek answers to the following questions: Does the presence of a hydride lens inevitably lead to rupture at a lower pressure? How does it mechanistically affect the crack initiation and propagation? The irradiated samples in our investigation were taken from the regions of the fuel cladding with oxide spallation. Subsequently, we used neutron radiography to further select samples covering a range of hydride blister sizes on which the burst testing was performed. Rupture pressure, hoop strength, and circumferential strain data will be reported. For each sample tested, detailed metallography and fractography were performed on 2-mm size sections containing the burst opening to provide insights into the mechanism of crack initiation and propagation. Local and mean hydrogen concentrations were measured. The paper will include and elucidate new details often not fully investigated by other burst test investigations reported in the open literature. In samples with multiple blisters, the crack initiates at the largest one, which also governs the fracture mode. Reduction in the rupture pressure can be simply correlated to the reduction in sample wall thickness excluding the blister (i.e., its remaining ligament). There is a lower bound on the blister size to have any influence on the rupture pressure. Further, local plastic circumferential strain at each blister can be correlated to relative hydride lens area, as projected onto the cladding surface.