Three potential clay materials for isolation of canisters containing high level radioactive waste (HLRW) were exposed to repository-like conditions with respect to water uptake and increased temperature for three weeks, and then allowed to become fully water saturated for determining the hydraulic conductivity and swelling pressure under room temperature conditions. Wyoming bentonite (MX-80) and Chinese bentonite (GMZ), which are both Na-dominated montmorillonitic clays, and German Friedland clay (FIM), which consists of mixed-layer illite/smectite, were used in the study. The experiment started with compaction of air-dry powder under the same pressure (1.30 MPa) in cells, followed by heating the cells at one end to 85–95 °C and circulating 3.5% CaCl2 solution through a filter at the opposite end, which was held at a constant temperature of about 50 °C for 3 weeks. After termination of the hydrothermal tests the samples were fluid saturated at room temperature and then sectioned for determining the hydraulic conductivity, swelling pressure, and compressibility of the least and most heated parts, and for investigation of micro-structural and mineralogical changes. The results showed that while FIM was not noticeably affected by the hydrothermal treatment, MX-80 and GMZ lost a significant part of the swelling pressure and experienced an obvious increase of hydraulic conductivity and stiffness. The most obvious chemical and mineralogical changes were an increase in Si content and the precipitation of silica, gypsum and kaolinite in the most heated parts of MX-80 and GMZ samples. The precipitation of silica was believed to be the cause of the stiffening.