Purpose: This study was carried out to verify the effect of adding macro-retentive axial grooves to conservative proximal cavities on the marginal sealing of resin composite restorations bonded with two different adhesive approaches.Materials and Methods: A total of one hundred and sixty freshly extracted caries-free human maxillary premolar teeth were selected for this study. All the teeth were embedded in specially designed cylindrical teflon molds. The teeth were divided into two main groups according to presence of macro-retentive features. Each group was divided into two subgroups according to the type of adhesive system (etch and rinse adhesive system or self-etch adhesive system). Each subgroup was divided into two classes according to cyclic loading. Each class was divided into two subclasses according to aging period. Standardized class II occluso-mesial (OM) or occluso-distal (OD) were prepared with the following dimensions (4 mm occluso-gingival, 3 mm bucco-lingual, 1.5 mm mesio-distal). Two vertical grooves with 0.5mm depth were prepared at the axio-buccal and axio-palatal line angles. Half of the specimens of each group were subjected to fatigue cyclic loading. A digital image analysis system was used to measure and qualitatively evaluate the degree of dye penetration along the gingival cavo-surface margin till the axial wall. Results: The results of this study revealed that groups with axial grooves recorded statistically significant higher microleakage mean values(1074.988 ± 281.6 µm) than the groups without axial grooves(780.2 ± 146.4 µm) . Etch and rinse groups recorded statistically significant higher microleakage mean values (971.5125 ± 320 µm) than self-etch groups (883.725 ± 165.1333 µm). The groups subjected to cyclic loading recorded statistically significant higher microleakage mean values (1620.35 ± 525.9878 µm) than non-cycled groups(234.8875 ± 83.9 µm). The groups aged for 3 months recorded statistically significant higher microleakage mean values (1343.45 ± 578.9 µm) than immediate groups(511.7875 ± 94.8 µm).Conclusions: (1)Adhesive cavity design without macro-retentive grooves is recommended for posterior compound resin composite restorations. (2)Self-etch adhesive approach has better cervical marginal sealing than etch and rinse one. (3)Repeated occlusal cyclic loading affected the marginal sealing of resin composite restorations. (4)Hydrolytic degradation of resin composite restorations is considered a critical issue in longevity of resin composite restorations.