BACKGROUND This in vitro study was conducted to compare the effect of universal bonding application strategy (i.e., self-etch and etch-and-rinse) on marginal adaptation of bulk-fill and conventional composite resins in Class II restorations. METHODS In this in vitro study sixty sound premolars extracted for orthodontic reasons were selected. The samples were allocated to four groups based on the universal bonding application strategy (self-etch and etch and rinse) and type of composite (bulk-fill and conventional). In each group, boxes were prepared with a depth of 4 mm on the mesial surfaces. Finally, the marginal adaptation of the samples was evaluated under a stereomicroscope. Two-way ANOVA was used to compare the marginal adaptation data in the study. Statistical significance was set at P < 0.05. RESULTS Considering the type of universal bonding application strategy, there was a statistically significant difference in marginal adaptation. Etch-and-rinse strategy showed better marginal adaptation compared to self-etch strategy (P < 0.001). However, there was no statistically significant difference in marginal adaptation between the two composite resins (P = 0.829). Furthermore, the interaction between the two factors (type of universal bonding application strategy and type of composite resin) was not statistically significant (P = 0.629). CONCLUSIONS Etch-and-rinse bonding application strategy in both the bulk-fill and conventional composite resins exhibited better marginal adaptation compared to self-etch bonding application strategy. However, the difference of marginal adaptation between the two types of composite resins (bulk and conventional) was not significant.