Objective: This prospective in vivo study aimed to compare the clinical behavior of a flowable composite resin (Genial Universal Flo, GC) and a nanohybrid universal composite resin (Tetric Evo Ceram, Ivoclar Vivadent) used in Class I and II direct esthetic restorations in posterior teeth. Methods: A total of 108 Class I and II direct restorations were performed in patients aged between 20 and 60 years. The originality of this study lies in the fact that both materials were placed in pairs, in the same clinical environment (i.e., the same patient and the same type of tooth). The evaluations were performed now of restoration and after 2-weeks, 6-, 12-, and 24-months intervals using clinical examination, clinical photographs, and radiological examination, according to modified USPHS criteria. Statistical analysis was performed using the Fisher exact test and chi-square analysis. Results: At baseline, the universal composite resin showed better esthetic properties such as surface luster, surface staining marginal staining. Both materials regressed significantly over time with no significant difference between groups. Conclusions: Both flowable and nanohybrid composite resins exhibit acceptable clinical performance. The present 24 months of evaluation of different composites showed that the G-ænial Universal Flo could be an effective esthetic material for posterior restoration. No significant difference between both materials over time concerning surface luster, surface staining, and marginal staining.