The objective of this study was to assess the bonding performance of a new universal self-adhesive cement RelyX Unicem (RXU) to dentin and enamel compared to four currently used luting systems, using a shear bond strength test with and without thermocycling. Median bond strengths were determined after 24 h storage, and after thermocycling (6,000 cycles, 5-55 degrees C) for RXU and compared to Syntac/Variolink II (SynC/V) as a standard for luting conventional ceramics, ED-Primer II/Panavia F2.0 (EDII/PF2), Prime and Bond NT/Dyract Cem Plus (PBNT/DyCP), and a glass ionomer cement, Ketac Cem (KetC), as a standard for luting high-strength ceramic and metal-based restorations. Data (n=10 per group) were statistically analyzed using the Mann-Whitney-Wilcoxon test at the 0.05 level of significance. The bond strength (MPa) of RXU to dentin (10.8) was not statistically different from those of SynC/V (15.1), EDII/PF2 (10.5) or PBNT/DyCP (10.1), and statistically higher than KetC (4.1). The bond strength of RXU to enamel (14.5) was significantly lower than those of SynC/V (32.8), EDII/PF2 (23.6), and PBNT/DyCP (17.8), but higher than KetC (6.1). After thermocycling, the bond strength of RXU to enamel significantly decreased, but was still significantly higher than that of KetC. RelyX Unicem may be considered an alternative to Ketac Cem for high-strength ceramic or metal-based restorations, and may be used for luting conventional ceramic crowns with little or no enamel left.