The aim of this in vivo study was to evaluate the interfacial marginal adaptation of a calcium aluminate cement, Doxadent (DD), and to compare it intra-individually with a resin composite, Tetric Ceram/Syntac Single-Component (TC/SS), in Class II cavities. Sixteen Class II box-shaped, enamel-bordered cavities were prepared in eight premolars scheduled to be extracted after 1months service for orthodontic reasons. The interfacial marginal adaptation (internal surfaces) of the restorations was evaluated by a quantitative scanning electron microscope analysis using a replica method. DD showed a statistically significant, lower degree of gap-free adaptation to enamel compared with TC/SS: 84% vs. 93%. To dentin, DD showed a significantly better adaptation than TC/SS: 72% vs. 49%. A high frequency of enamel fractures perpendicular to the margins was observed for the DD restorations, which may be explained by an expansion of the calcium-aluminate cement. It can be concluded that DD showed a better adaptation to dentin while TC/SS showed a better adaptation to enamel. The dimensional changes of DD have to be investigated before clinical use can be recommended.