This study evaluated the fracture resistance of cusp replacing direct resin composite restorations (DCR) in premolars that had been previously filled with amalgam mesial–occlusal–distal (MOD) restorations and compared their fracture resistance with those made on sound dentin and intact teeth. Recently extracted human premolars with either MOD amalgam restorations or sound/intact ones were selected for the study. Cavities with cusp reduction were made for the following groups: (a) Group 1: DCRs on previously amalgam-affected dentin (n = 11), (b) Group 2: DCRs on sound dentin (n = 10), and (c) Group 3: intact premolars (n = 9). Teeth in Groups 1 and 2 were restored with a 3-step etch and rinse adhesive (Quadrant Unibond) and filled with hybrid composite (Clearfil Photo Posterior). All specimens were thermocycled for 5000 cycles (5–55 °C). The buccal cusps of the teeth were loaded until fracture under compression at 45° to the long axis of the teeth in a universal testing machine (1 mm/min). Data (N) were statistically analyzed using one-way ANOVA and Student’s t-test (α = 0.01). Intact teeth (Group 3) showed significantly higher fracture resistance (893 ± 196) compared to both restored groups (p < 0.01). No significant difference was found between the DCRs made on amalgam-affected dentin (Group 1: 607 ± 166) and sound dentin (Group 2: 588 ± 183) (p > 0.01). More than half of the teeth of Groups 2 and 3 showed unrepairable fractures with pulp exposure.