OBJECTIVE This study aims to evaluate the effect of a minimally invasive mesial-occlusal-distal (mod) preparation on the marginal adaptation of ceramic and composite inlays with the aim of saving sound dental substance. METHODS Class II mod cavities were prepared in 50 extracted human molars and randomly allocated to five groups (n = 10). In all groups, the mesial-proximal box margins were located in the dentin, 1 mm below the cementoenamel junction (CEJ), while the distal box margins were 1 mm above the CEJ. In groups A and B, conventional standard preparations with a divergent angle of α = 6° were prepared. In groups C, D, and E, minimally invasive standard preparations with a convergent angle of α = 10° were prepared. In groups A and D, composite inlays and, in groups B and C, ceramic inlays were fabricated (chairside economical restoration of esthetic ceramics (CEREC)) and adhesively inserted. In group E, a direct composite filling using the incremental technique was placed. Replicas were taken before and after thermomechanical loading (1,200,000 cycles, 50/5 °C, max. load 49 N). Marginal integrity (tooth-luting composite, luting composite-inlay) was evaluated by scanning electron microscopy (× 200). The percentage of continuous margins in the different locations was compared between and within groups before and after cycling, using ANOVA and Scheffé post hoc test. RESULTS After the thermomechanical loading, no significant differences were observed between the different groups with respect to the interface of luting composite-inlay. At the interface of tooth-luting composite for preparations involving the dentin, groups A and B behaved significantly better compared to the control group E, which in turn were not different to groups C and D. CONCLUSIONS Composite and ceramic inlays inserted in minimally invasive prepared mod cavities result in margins not different from those of inlays placed in conventional mod preparations. Direct composite filling margins, however, were inferior to those attained by conventional indirect restorations. CONCLUSIONS Minimally invasive preparations for mod inlays with undercuts show marginal adaptation equal to that of conventional inlay preparation design.