Sorbent-enhanced steam methane reforming (SE-SMR) is an emerging technology for the production of high-purity hydrogen from hydrocarbons with in situ CO2 capture. Here, SE-SMR was studied using a mixture containing a Ni-hydrotalcite-derived catalyst and a synthetic, Ca-based, calcium aluminate supported CO2 sorbent. The fresh and cycled materials were characterized using N2 physisorption, X-ray diffraction, and scanning and transmission electron microscopy. The combination of a Ni-hydrotalcite catalyst and the synthetic CO2 sorbent produced a stream of high-purity hydrogen, that is, 99 vol % (H2O- and N2-free basis). The CaO conversion of the synthetic CO2 sorbent was 0.58 mol CO2/mol CaO after 10 cycles, which was more than double the value achieved by limestone. The favorable CO2 capture characteristics of the synthetic CO2 sorbent were attributed to the uniform dispersion of CaO on a stable nanosized mayenite framework, thus retarding thermal sintering of the material. On the other hand, the cycled limestone lost its nanostructured morphology completely over 10 SE-SMR cycles due to its intrinsic lack of a support component.