Objectives: The aim of the present study was to determine the effect of two conditioning methods, phosphoric acid and XeCl laser application on microleakage at composite resin restorations. Methods: Class II MOD (mesio-occluso-distal) cavities were prepared on 90 extracted human wisdom teeth with one proximogingival margin on enamel and the other on dentin. Phosphoric acid (37%) and a XeCl excimer laser system were used for the etching procedure. The prepared teeth were randomly assigned to six groups: In group 1, acid-etching of the enamel margins was followed by application of enamel bonding, in group 2 additionally a dentin bonding system was used. In group 3, acid-etching of the enamel and dentin (total etch) was followed by the application of dentin bonding. In group 4, laser-etching of enamel margins was followed by the application of enamel bonding, in group 5 dentin bonding was used additionally. In group 6, laser-etching of enamel and dentin margins was followed by the application of dentin bonding. All restorations were placed incrementally and polymerized with a halogen light source. After restoration, all samples were thermocycled and stained in 0.5% basic fuchsin and sectioned longitudinally in a mesio-distal plane. Microleakage was scored by means of a stereomicroscope. The margins of the restorations at tooth-resin interface were examined with a scanning electron microscope. Results: In all groups, marginal leakage was more extensive at the gingival margin that was in dentin than at the gingival margin in enamel. Microleakage scores and the gap at the tooth-resin interface were significantly lower in all acid-etched groups than in laser-etched groups. Conclusion: Acid-etch technique is more effective than the investigated laser-etch technique at 308 nm concerning the reduction of marginal leakage in composite restorations.